Development of D-melittin polymeric nanoparticles for anti-cancer treatment

Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomi...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Lv, Shixian [verfasserIn] Sylvestre, Meilyn [verfasserIn] Song, Kefan [verfasserIn] Pun, Suzie H. [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates

Übergeordnetes Werk:	Enthalten in: Biomaterials - Amsterdam [u.a.] : Elsevier Science, 1980, 277
Übergeordnetes Werk:	volume:277

DOI / URN:	10.1016/j.biomaterials.2021.121076

Katalog-ID:	ELV006668518

Internformat


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520			\|a Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens.
650		4	\|a Anti-cancer peptide
650		4	\|a Melittin
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650		4	\|a Polymeric micelles
650		4	\|a Polymer-peptide conjugates
700	1		\|a Sylvestre, Meilyn \|e verfasserin \|0 (orcid)0000-0002-4162-9388 \|4 aut
700	1		\|a Song, Kefan \|e verfasserin \|4 aut
700	1		\|a Pun, Suzie H. \|e verfasserin \|0 (orcid)0000-0003-1443-4996 \|4 aut
773	0	8	\|i Enthalten in \|t Biomaterials \|d Amsterdam [u.a.] : Elsevier Science, 1980 \|g 277 \|h Online-Ressource \|w (DE-627)32043320X \|w (DE-600)2004010-6 \|w (DE-576)098614932 \|x 0142-9612 \|7 nnns
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912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
936	b	k	\|a 44.09 \|j Medizintechnik
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952			\|d 277

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publishDate	2021
allfields	10.1016/j.biomaterials.2021.121076 doi (DE-627)ELV006668518 (ELSEVIER)S0142-9612(21)00432-4 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Lv, Shixian verfasserin aut Development of D-melittin polymeric nanoparticles for anti-cancer treatment 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens. Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates Sylvestre, Meilyn verfasserin (orcid)0000-0002-4162-9388 aut Song, Kefan verfasserin aut Pun, Suzie H. verfasserin (orcid)0000-0003-1443-4996 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 277 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:277 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 277
spelling	10.1016/j.biomaterials.2021.121076 doi (DE-627)ELV006668518 (ELSEVIER)S0142-9612(21)00432-4 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Lv, Shixian verfasserin aut Development of D-melittin polymeric nanoparticles for anti-cancer treatment 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens. Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates Sylvestre, Meilyn verfasserin (orcid)0000-0002-4162-9388 aut Song, Kefan verfasserin aut Pun, Suzie H. verfasserin (orcid)0000-0003-1443-4996 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 277 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:277 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 277
allfields_unstemmed	10.1016/j.biomaterials.2021.121076 doi (DE-627)ELV006668518 (ELSEVIER)S0142-9612(21)00432-4 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Lv, Shixian verfasserin aut Development of D-melittin polymeric nanoparticles for anti-cancer treatment 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens. Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates Sylvestre, Meilyn verfasserin (orcid)0000-0002-4162-9388 aut Song, Kefan verfasserin aut Pun, Suzie H. verfasserin (orcid)0000-0003-1443-4996 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 277 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:277 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 277
allfieldsGer	10.1016/j.biomaterials.2021.121076 doi (DE-627)ELV006668518 (ELSEVIER)S0142-9612(21)00432-4 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Lv, Shixian verfasserin aut Development of D-melittin polymeric nanoparticles for anti-cancer treatment 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens. Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates Sylvestre, Meilyn verfasserin (orcid)0000-0002-4162-9388 aut Song, Kefan verfasserin aut Pun, Suzie H. verfasserin (orcid)0000-0003-1443-4996 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 277 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:277 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 277
allfieldsSound	10.1016/j.biomaterials.2021.121076 doi (DE-627)ELV006668518 (ELSEVIER)S0142-9612(21)00432-4 DE-627 ger DE-627 rda eng 570 DE-600 BIODIV DE-30 fid 44.09 bkl Lv, Shixian verfasserin aut Development of D-melittin polymeric nanoparticles for anti-cancer treatment 2021 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens. Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates Sylvestre, Meilyn verfasserin (orcid)0000-0002-4162-9388 aut Song, Kefan verfasserin aut Pun, Suzie H. verfasserin (orcid)0000-0003-1443-4996 aut Enthalten in Biomaterials Amsterdam [u.a.] : Elsevier Science, 1980 277 Online-Ressource (DE-627)32043320X (DE-600)2004010-6 (DE-576)098614932 0142-9612 nnns volume:277 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-BIODIV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_150 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.09 Medizintechnik AR 277
language	English
source	Enthalten in Biomaterials 277 volume:277
sourceStr	Enthalten in Biomaterials 277 volume:277
format_phy_str_mv	Article
bklname	Medizintechnik
institution	findex.gbv.de
topic_facet	Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates
dewey-raw	570
isfreeaccess_bool	false
container_title	Biomaterials
authorswithroles_txt_mv	Lv, Shixian @@aut@@ Sylvestre, Meilyn @@aut@@ Song, Kefan @@aut@@ Pun, Suzie H. @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	32043320X
dewey-sort	3570
id	ELV006668518
language_de	englisch
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author	Lv, Shixian
spellingShingle	Lv, Shixian ddc 570 fid BIODIV bkl 44.09 misc Anti-cancer peptide misc Melittin misc Drug delivery misc Polymeric micelles misc Polymer-peptide conjugates Development of D-melittin polymeric nanoparticles for anti-cancer treatment
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topic_title	570 DE-600 BIODIV DE-30 fid 44.09 bkl Development of D-melittin polymeric nanoparticles for anti-cancer treatment Anti-cancer peptide Melittin Drug delivery Polymeric micelles Polymer-peptide conjugates
topic	ddc 570 fid BIODIV bkl 44.09 misc Anti-cancer peptide misc Melittin misc Drug delivery misc Polymeric micelles misc Polymer-peptide conjugates
topic_unstemmed	ddc 570 fid BIODIV bkl 44.09 misc Anti-cancer peptide misc Melittin misc Drug delivery misc Polymeric micelles misc Polymer-peptide conjugates
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title	Development of D-melittin polymeric nanoparticles for anti-cancer treatment
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title_full	Development of D-melittin polymeric nanoparticles for anti-cancer treatment
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author_browse	Lv, Shixian Sylvestre, Meilyn Song, Kefan Pun, Suzie H.
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title_sort	development of d-melittin polymeric nanoparticles for anti-cancer treatment
title_auth	Development of D-melittin polymeric nanoparticles for anti-cancer treatment
abstract	Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens.
abstractGer	Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens.
abstract_unstemmed	Melittin, the primary peptide component of bee venom, is a potent cytolytic anti-cancer peptide with established anti-tumor activity. However, practical application of melittin in oncology is hampered by its strong, nonspecific hemolytic activity and intrinsic instability. To address these shortcomings, delivery systems are used to overcome the drawbacks of melittin and facilitate its safe delivery. Yet, a recent study revealed that encapsulated melittin remains immunogenic and can act as an adjuvant to elicit a fatal antibody immune response against the delivery carrier. We discovered that substitution of l-amino acids with d-amino acids mitigates this problem: D-melittin nanoformulations induce significantly decreased immune response, resulting in excellent safety without compromising cytolytic potential. We now report the first application of D-melittin and its micellar formulations for cancer treatment. D-melittin was delivered by a pH-sensitive polymer carrier that (i) forms micellar nanoparticles at normal physiological conditions, encapsulating melittin, and (ii) dissociates at endosomal pH, restoring melittin activity. D-melittin micelles (DMM) exhibits significant cytotoxicity and induces hemolysis in a pH-dependent manner. In addition, DMM induce immunogenic cell death, revealing its potential for cancer immunotherapy. Indeed, in vivo studies demonstrated the superior safety profile of DMM over free peptide and improved efficacy at prohibiting tumor growth. Overall, we present the first application of micellar D-melittin for cancer therapy. These findings establish a new strategy for safe, systemic delivery of melittin, unlocking a potential pathway toward clinical translation for cytotoxic peptides as anti-cancer agents. which can revolutionize in vivo delivery of therapeutic peptides and peptide antigens.
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title_short	Development of D-melittin polymeric nanoparticles for anti-cancer treatment
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up_date	2024-07-06T22:09:42.131Z
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Development of D-melittin polymeric nanoparticles for anti-cancer treatment

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