Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery

Abstract

Mitochondrial-targeting therapy is considered an important strategy for cancer treatment. (3-Carboxypropyl) triphenyl phosphonium (CTPP) is one of the candidate molecules that can drive drugs or nanomedicines to target mitochondria via electrostatic interactions. However, the mitochondrial-targeting effectiveness of CTPP is low. Therefore, pH-sensitive polymer–liposome complexes with charge-conversion copolymers and CTPP-containing cationic liposomes were designed for efficiently delivering an anti-cancer agent, ceramide, into cancer cellular mitochondria. The charge-conversion copolymers, methoxypoly(ethylene glycol)-block-poly(methacrylic acid-g-histidine), were anionic and helped in absorbing and shielding the positive charges of cationic liposomes at pH 7.4. In contrast, charge-conversion copolymers became neutral in order to depart from cationic liposomes and induced endosomal escape for releasing cationic liposomes into cytosol at acidic endosomes. The experimental results reveal that these pH-sensitive polymer–liposome complexes could rapidly escape from MCF-7 cell endosomes and target MCF-7 mitochondria within 3 h, thereby leading to the generation of reactive oxygen species and cell apoptosis. These findings provide a promising solution for cationic liposomes in cancer mitochondrial-targeting drug delivery.

Lipopolyplex-Mediated Co-Delivery of Doxorubicin and FAK siRNA to Enhance Therapeutic Efficiency of Treating Colorectal Cancer

“…To observe the biodistribution of DLP, we first prepared DLP using synthesized cholesterol-NH2 instead of cholesterol and then conjugated Cy5.5 into DLP via a substitution reaction of amino groups from cholesterol with NHS ester from Cy5.5. The synthesis method of cholesterol-NH2 was the same as our previous report [ 36 ]. After 4 weeks of tumor growth (>500 mm 3 ) and the tail vein of the tumor-bearing BALB/c nude mice was intravenously (i.v.)…”

Strategies for Targeted Delivery via Structurally Variant Polymeric Nanocarriers

“…[104] Polymer-liposomes have further been grafted with enzyme sensitive sensors, viz.,the Programmed Cell Death Ligand 1 (PD-L1) inhibitor and matrix metalloproteinases (MMPs), to develop pH and enzyme dual responsive delivery systems for cancer immunotherapy. [105] Polymer-liposome complexes have been used in mitochondrial delivery, [106] vaccine stabilization [107] and in other biomedical applications as well. [108] Variation in liposomal compositions is done with emphasis on particular modes of administration.…”

Cancer Cell Models for the Development of Anti-Cancer Drugs

“…It was most gratifying to note enthusiastic response from all the contributors for submitting manuscripts containing excellent research in multi-disciplinary areas relevant to novel anti-cancer drugs and innovative methodology for drug delivery. Specifically, experimental approaches utilizing 3D bio-printing [2,3], liposome-mediated drug delivery [4], functional significance of estrogen receptors in initial events relevant to breast cancer development [5] and the development of models for drug-resistant colon cancer stem cells [6] provide strong evidence for innovative application of state-of-the art technology.…”