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.

A Facile Low-Dose Photosensitizer-Incorporated Dissolving Microneedles-Based Composite System for Eliciting Antitumor Immunity and the Abscopal Effect

“…In recent years, easy-to-synthesize and environmentally friendly carrier-free nanodelivery systems have gradually been favored by researchers. Among these, self-nanoassemblies formed by free drugs and hydrophobic carriers exhibited enhanced water solubility but also a certain level of systemic toxicity . Inspired by the squalenoylation-based self-assembly method, which has been successfully used in the synthesis of nanocomposites of chemotherapy drugs (doxorubicin, gemcitabine, etc.…”

“…Among these, self-nanoassemblies formed by free drugs and hydrophobic carriers exhibited enhanced water solubility but also a certain level of systemic toxicity. 8 Inspired by the squalenoylation-based self-assembly method, which has been successfully used in the synthesis of nanocomposites of chemotherapy drugs (doxorubicin, gemcitabine, etc. ), 9−11 we previously exploited naturally abundant polyunsaturated fatty acids (PUFAs) for the conjugation of chlorin e6 (Ce6) through covalent bonding, thereby facilitating self-assembly of Ce6 in water into nanoassemblies (L-Ce6 NAs).…”

Self-assembled Natural Product-based Carrier-free Nanoplatforms for Efficient Bioactivity

“…Cabazitaxel (CTX), the PTX derivative, could interact with dasatinib (DAS) to form nanoassemblies. 78 DAS with amphiphilicity drove the nano-assembly of the CTX-DAS nanoparticles without any exogenous excipients. The nano-assemblies exhibited 100% drug loading and aggregation-induced emission at 422 nm for tumor diagnosis.…”

How to improve photodynamic therapy-induced antitumor immunity for cancer treatment?

“…It is worth mentioning that the immune checkpoints have been shown to have a great prospect in cancer treatment, and their combination with PDT improves the prognosis of cancer and provides better control and effect for anti-tumor immunity 20 . Additionally, PDT combined with other methods (such as photothermal therapy (PTT) 6 , 21 , chemotherapy 22 - 24 , and radiotherapy 25 ) can better increase the recruitment of dendritic cells (DCs), promote the development of CD8 + T cells, regulate the TME, and activate host immune function.…”