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Calcium-mineralized polypeptide nanoparticle for intracellular drug delivery in osteosarcoma chemotherapy.

ABSTRACT: The acidic microenvironments of tumor tissue and cells provide an opportunity for the development of pH-responsive drug delivery systems in cancer therapy. In this work, we designed a calcium carbonate (CaCO3)-core-crosslinked nanoparticle of methoxy poly(ethylene glycol)-block-poly(l-glutamic acid) through mineralization for intracellular delivery of doxorubicin (DOX), referred to as CaNP/DOX. CaNP/DOX exhibited high drug loading capability, uniform nanoparticle size, and pH-dependent DOX release. In the meantime, the enhanced cell uptake, superior cytotoxicity toward mouse osteosarcoma K7 cells, extended circulation half-life, and improved accumulation of DOX in K7 allograft tumor from CaNP/DOX were also demonstrated. More interestingly, CaNP/DOX displayed improved antitumor effect and reduced side effects against the K7 osteosarcoma-allografted mouse model and the 143B orthotopic osteosarcoma mouse model. Given the superior properties of Ca-mineralized polypeptide nanoparticle for intracellular drug delivery, the smart drug delivery system showed strong competitiveness in clinical chemotherapy of cancers.

SUBMITTER: Li K

PROVIDER: S-EPMC7298657 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Calcium-mineralized polypeptide nanoparticle for intracellular drug delivery in osteosarcoma chemotherapy.

Li Ke K Li Di D Zhao Li L Chang Yonghe Y Zhang Yi Y Cui Yan Y Zhang Zhiyu Z

Bioactive materials 20200612 3

The acidic microenvironments of tumor tissue and cells provide an opportunity for the development of pH-responsive drug delivery systems in cancer therapy. In this work, we designed a calcium carbonate (CaCO3)-core-crosslinked nanoparticle of methoxy poly(ethylene glycol)-block-poly(l-glutamic acid) through mineralization for intracellular delivery of doxorubicin (DOX), referred to as CaNP/DOX. CaNP/DOX exhibited high drug loading capability, uniform nanop ...[more]

PMID: 32596554

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Project description:The use of dexamethasone for eye disease treatment is limited by its low solubility, bioavailability, and rapid elimination when applied topically. The covalent conjugation of dexamethasone with polymeric carriers is a promising strategy to overcome existing drawbacks. In this work, amphiphilic polypeptides capable of self-assembly into nanoparticles were proposed as potential delivery systems for intravitreal delivery. The nanoparticles were prepared and characterized using poly(L-glutamic acid-co-D-phenylalanine) and poly(L-lysine-co-D/L-phenylalanine) as well as poly(L-lysine-co-D/L-phenylalanine) covered with heparin. The critical association concentration for the polypeptides obtained was in the 4.2-9.4 μg/mL range. The hydrodynamic size of the formed nanoparticles was between 90 and 210 nm, and they had an index of polydispersity between 0.08 and 0.27 and an absolute zeta-potential value between 20 and 45 mV. The ability of nanoparticles to migrate in the vitreous humor was examined using intact porcine vitreous. Conjugation of DEX with polypeptides was performed by additional succinylation of DEX and activation of carboxyl groups introduced to react with primary amines in polypeptides. The structures of all intermediate and final compounds were verified by 1H NMR spectroscopy. The amount of conjugated DEX can be varied from 6 to 220 µg/mg of polymer. The hydrodynamic diameter of the nanoparticle-based conjugates was increased to 200-370 nm, depending on the polymer sample and drug loading. The release of DEX from the conjugates due to hydrolysis of the ester bond between DEX and the succinyl moiety was studied both in a buffer medium and a vitreous/buffer mixture (50/50, v/v). As expected, the release in the vitreous medium was faster. However, the release rate could be controlled in the range of 96-192 h by varying the polymer composition. In addition, several mathematical models were used to assess the release profiles and figure out how DEX is released.

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Calcium-mineralized polypeptide nanoparticle for intracellular drug delivery in osteosarcoma chemotherapy.

Publications

Calcium-mineralized polypeptide nanoparticle for intracellular drug delivery in osteosarcoma chemotherapy.

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