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Quantitative self-assembly of pure drug cocktails as injectable nanomedicines for synergistic drug delivery and cancer therapy.

ABSTRACT: New strategies to fabricate nanomedicines with high translational capacity are urgently desired. Herein, a new class of self-assembled drug cocktails that addresses the multiple challenges of manufacturing clinically useful cancer nanomedicines was reported. Methods: With the aid of a molecular targeted agent, dasatinib (DAS), cytotoxic cabazitaxel (CTX) forms nanoassemblies (CD NAs) through one-pot process, with nearly quantitative entrapment efficiency and ultrahigh drug loading of up to 100%. Results: Surprisingly, self-assembled CD NAs show aggregation-induced emission, enabling particle trafficking and drug release in living cells. In preclinical models of human cancer, including a patient-derived melanoma xenograft, CD NAs demonstrated striking therapeutic synergy to produce a durable recession in tumor growth. Impressively, CD NAs alleviated the toxicity of the parent CTX agent and showed negligible immunotoxicity in animals. Conclusions: Overall, this approach does not require any carrier matrices, offering a scalable and cost-effective methodology to create a new generation of nanomedicines for the safe and efficient delivery of drug combinations.

SUBMITTER: Chen X

PROVIDER: S-EPMC8058735 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Quantitative self-assembly of pure drug cocktails as injectable nanomedicines for synergistic drug delivery and cancer therapy.

Chen Xiaona X Xie Binbin B Huang Lingling L Wan Jianqin J Wang Yuchen Y Shi Xiaowei X Qiao Yiting Y Song Haihan H Wang Hangxiang H

Theranostics 20210331 12

New strategies to fabricate nanomedicines with high translational capacity are urgently desired. Herein, a new class of self-assembled drug cocktails that addresses the multiple challenges of manufacturing clinically useful cancer nanomedicines was reported. <b>Methods:</b> With the aid of a molecular targeted agent, dasatinib (DAS), cytotoxic cabazitaxel (CTX) forms nanoassemblies (<b>CD NAs</b>) through one-pot process, with nearly quantitative entrapment efficiency and ultrahigh drug loading ...[more]

PMID: 33897877

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Project description:A two-component injectable hydrogel was suitably prepared for the encapsulation and prolonged release of tilorone which is an antimuscular atrophy drug. The rapid (7-45 s, depending on the polymer concentration) in situ solidifications of the hydrogel were evoked by the evolving Schiff-base bonds between the aldehyde groups of modified PVA (4-formyl benzoate PVA, PVA-CHO, 5.9 mol% functionalization degree) and the amino groups of 3-mercaptopropionate chitosan (CHIT-SH). The successful modification of the initial polymers was confirmed by both FTIR and NMR measurements; moreover, a new peak appeared in the FTIR spectrum of the 10% w/v PVA-CHO/CHIT-SH hydrogel at 1647 cm-1, indicating the formation of a Schiff base (-CH=N-) and confirming the interaction between the NH2 groups of CHIT-SH and the CHO groups of PVA-CHO for the formation of the dynamic hydrogel. The reaction between the NH2 and CHO groups of the modified biopolymers resulted in a significant increase in the hydrogel's viscosity which was more than one thousand times greater (9800 mPa·s) than that of the used polymer solutions, which have a viscosity of only 4.6 and 5.8 mPa·s, respectively. Furthermore, the initial chitosan was modified with mercaptopropionic acid (thiol content = 201.85 ± 12 µmol/g) to increase the mucoadhesive properties of the hydrogel. The thiolated chitosan showed a significant increase (~600 mN/mm) in adhesion to the pig intestinal membrane compared to the initial one (~300 mN/mm). The in vitro release of tilorone from the hydrogel was controlled with the crosslinking density/concentration of the hydrogel; the 10% w/v PVA-CHO/CHIT-SH hydrogel had the slowest releasing (21.7 h-1/2) rate, while the 2% w/v PVA-CHO/CHIT-SH hydrogel had the fastest releasing rate (34.6 h-1/2). Due to the characteristics of these hydrogels, their future uses include tissue regeneration scaffolds, wound dressings for skin injuries, and injectable or in situ forming drug delivery systems. Eventually, we hope that the developed hydrogel will be useful in the local treatment of muscle atrophy, such as laryngotracheal atrophy.

Dataset Information

Quantitative self-assembly of pure drug cocktails as injectable nanomedicines for synergistic drug delivery and cancer therapy.

Publications

Quantitative self-assembly of pure drug cocktails as injectable nanomedicines for synergistic drug delivery and cancer therapy.

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