Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol...Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol)-b-poly(L-aspartic acid)(PLD-b-PEG-b-PLD),spontaneously self-assembled with doxorubicin(DOX)via electrostatic interactions to form spherical micelles with a particle size of 60e80 nm(triblock ionomer complexes micelles,TBIC micelles).These micelles exhibited a high loading capacity of 70%(w/w)at a drug/polymer ratio of 0.5 at pH 7.0.They showed pH-responsive release patterns,with higher release at acidic pH than at physiological pH.Furthermore,DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line.Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis.These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats.Overall,these findings indicate that PLDb-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.展开更多
Chemo-resistance has pushed cancer treatment to the boundary of failure.This challenge has encouraged scientists to look for nanotechnological solutions.In this study,we have taken this goal one step further without d...Chemo-resistance has pushed cancer treatment to the boundary of failure.This challenge has encouraged scientists to look for nanotechnological solutions.In this study,we have taken this goal one step further without depending on chemotherapy.Specifically,hybrid metal,polymer,and lipid nanoparticles that formed an IR780-a photosensitizer and Zinc copper oxide incorporated nanoparticle(ZCNP)nanoparticles were utilized in a combined photothermal and photodynamic therapy.Through the mediation of triphenylphosphonium(TPP)as a mitochondria-targeting moiety,TPP-conjugated polymer-lipid hybrid nanoparticles containing ZCNP/IR-780 significantly enhanced cellular uptake by cancer cells and selectively targeted the mitochondria,which improved the induction of apoptosis.In tumor-bearing mice,the nanoparticles were detected predominantly in tumors rather than in the other principle organs,which did not show notable signs of toxicity.Both in vitro and in vivo results demonstrated a great improvement in photothermal and photodynamic efficacy in combination when compared to either one individually,and a significant inhibition of tumor growth was observed with the combined therapies.In summary,this study describes an effective mitochondria-targeting nanocarrier for the treatment of cancer using combined photothermal and photodynamic therapies.展开更多
基金This research was supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Education,Science and Technology(No.2012R1A2A2A02044997 and No.2012R1A1A1039059).
文摘Polyelectrolyte complex micelles were prepared by self-assembly of polypeptide-based triblock copolymer as a new drug carrier for cancer chemotherapy.The triblock copolymer,poly(L-aspartic acid)-b-poly(ethylene glycol)-b-poly(L-aspartic acid)(PLD-b-PEG-b-PLD),spontaneously self-assembled with doxorubicin(DOX)via electrostatic interactions to form spherical micelles with a particle size of 60e80 nm(triblock ionomer complexes micelles,TBIC micelles).These micelles exhibited a high loading capacity of 70%(w/w)at a drug/polymer ratio of 0.5 at pH 7.0.They showed pH-responsive release patterns,with higher release at acidic pH than at physiological pH.Furthermore,DOX-loaded TBIC micelles exerted less cytotoxicity than free DOX in the A-549 human lung cancer cell line.Confocal microscopy in A-549 cells indicated that DOX-loaded TBIC micelles were transported into lysosomes via endocytosis.These micelles possessed favorable pharmacokinetic characteristics and showed sustained DOX release in rats.Overall,these findings indicate that PLDb-PEG-b-PLD polypeptide micelles are a promising approach for anti-cancer drug delivery.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP)(No.2018R1A2A2A05021143)the Medical Research Center Program(2015R1A5A2009124)Support Center for Natural Products and Medical Materials(CRCNM)for technical support regarding the nano-indentation test。
文摘Chemo-resistance has pushed cancer treatment to the boundary of failure.This challenge has encouraged scientists to look for nanotechnological solutions.In this study,we have taken this goal one step further without depending on chemotherapy.Specifically,hybrid metal,polymer,and lipid nanoparticles that formed an IR780-a photosensitizer and Zinc copper oxide incorporated nanoparticle(ZCNP)nanoparticles were utilized in a combined photothermal and photodynamic therapy.Through the mediation of triphenylphosphonium(TPP)as a mitochondria-targeting moiety,TPP-conjugated polymer-lipid hybrid nanoparticles containing ZCNP/IR-780 significantly enhanced cellular uptake by cancer cells and selectively targeted the mitochondria,which improved the induction of apoptosis.In tumor-bearing mice,the nanoparticles were detected predominantly in tumors rather than in the other principle organs,which did not show notable signs of toxicity.Both in vitro and in vivo results demonstrated a great improvement in photothermal and photodynamic efficacy in combination when compared to either one individually,and a significant inhibition of tumor growth was observed with the combined therapies.In summary,this study describes an effective mitochondria-targeting nanocarrier for the treatment of cancer using combined photothermal and photodynamic therapies.
