Dataset Information

Self-Assembling pH-Responsive Nanoparticle Platform Based on Pectin-Doxorubicin Conjugates for Codelivery of Anticancer Drugs.

ABSTRACT: Pharmaceutical science based on biological nanotechnology is developing rapidly in parallel with the development of nanomaterials and nanotechnology in general. Pectin is a natural polysaccharide obtainable from a wide range of sources. Here, we show that doxorubicin (DOX)-conjugated hydrophilic pectin (PET) comprising an amphiphilic polymer loaded with hydrophobic dihydroartemisinin (DHA) self-assemble into nanoparticles. Importantly, conjugated DOX and DHA could be released quickly in a weakly acidic environment by cleavage of the acid-sensitive acyl hydrazone bond. Confocal microscopy and flow cytometry confirmed that these PET-DOX/DHA nanoparticles efficiently delivered DOX into the nuclei of MCF-7 cells. Significant tumor growth reduction was monitored in a female C57BL/6 mouse model, showing that the PET-DOX/DHA nanoparticle-mediated drug delivery system inhibited tumor growth and may improve therapy. Thus, we have demonstrated that pectin may be useful in the design of materials for biomedical applications.

SUBMITTER: Tao Y

PROVIDER: S-EPMC8153661 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Self-Assembling pH-Responsive Nanoparticle Platform Based on Pectin-Doxorubicin Conjugates for Codelivery of Anticancer Drugs.

Tao Yinghua Y Zheng Dan D Zhao Jingyang J Liu Kefeng K Liu Jing J Lei Jiandu J Wang Luying L

ACS omega 20210408 15

Pharmaceutical science based on biological nanotechnology is developing rapidly in parallel with the development of nanomaterials and nanotechnology in general. Pectin is a natural polysaccharide obtainable from a wide range of sources. Here, we show that doxorubicin (DOX)-conjugated hydrophilic pectin (PET) comprising an amphiphilic polymer loaded with hydrophobic dihydroartemisinin (DHA) self-assemble into nanoparticles. Importantly, conjugated DOX and DHA could be released quickly in a weakly ...[more]

PMID: 34056155

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Project description:BackgroundSmall interfering RNA (siRNA) is utilized as a potent agent for cancer therapy through regulating the expression of genes associated with tumors. While the widely application of siRNAs in cancer treatment is severely limited by their insufficient biological stability and its poor ability to penetrate cell membranes. Targeted delivery systems hold great promise to selectively deliver loaded drug to tumor site and reduce toxic side effect. However, the elevated tumor interstitial fluid pressure and efficient cytoplasmic release are still two significant obstacles to siRNA delivery. Co-delivery of chemotherapeutic drugs and siRNA represents a potential strategy which may achieve synergistic anticancer effect. Herein, we designed and synthesized a dual pH-responsive peptide (DPRP), which includes three units, a cell-penetrating domain (polyarginine), a polyanionic shielding domain (ehG)n, and an imine linkage between them. Based on the DPRP surface modification, we developed a pH-responsive liposomal system for co-delivering polo-like kinase-1 (PLK-1) specific siRNA and anticancer agent docetaxel (DTX), D-Lsi/DTX, to synergistically exhibit anti-tumor effect.ResultsIn contrast to the results at the physiological pH (7.4), D-Lsi/DTX lead to the enhanced penetration into tumor spheroid, the facilitated cellular uptake, the promoted escape from endosomes/lysosomes, the improved distribution into cytoplasm, and the increased cellular apoptosis under mildly acidic condition (pH 6.5). Moreover, both in vitro and in vivo study indicated that D-Lsi/DTX had a therapeutic advantage over other control liposomes. We provided clear evidence that liposomal system co-delivering siPLK-1 and DTX could significantly downregulate expression of PLK-1 and inhibit tumor growth without detectable toxic side effect, compared with siPLK-1-loaded liposomes, DTX-loaded liposomes, and the combinatorial administration.ConclusionThese results demonstrate great potential of the combined chemo/gene therapy based on the multistage pH-responsive codelivery liposomal platform for synergistic tumor treatment.

Dataset Information

Self-Assembling pH-Responsive Nanoparticle Platform Based on Pectin-Doxorubicin Conjugates for Codelivery of Anticancer Drugs.

Publications

Self-Assembling pH-Responsive Nanoparticle Platform Based on Pectin-Doxorubicin Conjugates for Codelivery of Anticancer Drugs.

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