Coordination-Driven Self-Assembly of Biomedicine to Enhance Photodynamic Therapy by Inhibiting Proteasome and Bcl-2

by Selleckchem | Oct 16 2023

Tumor cells resist oxidative damage and apoptosis by activating defense mechanisms. Herein, a self-delivery biomedicine (designated as BSC) is developed by the self-assembly of Bortezomib (BTZ), Sabutoclax (Sab) and Chlorin e6 (Ce6). Interestingly, BTZ can be coordinated with Sab to promote the assembly of uniform ternary biomedicine through non-covalent intermolecular interactions. Moreover, BTZ as a proteasome inhibitor can prevent tumor cells from scavenging damaged proteins to reduce their oxidative resistance. Sab can downregulate B-cell lymphoma 2 (Bcl-2) to decrease the antiapoptotic protein. Both the proteasome and Bcl-2 inhibitions contribute to increasing cell apoptosis and amplifying photodynamic therapy (PDT) efficacy of Ce6. Encouragingly, carrier-free BSC receives all biological activities of these assembly elements, including photodynamic performance as well as inhibitory capabilities of proteasome and Bcl-2. Besides, BSC has a preferable cellular uptake ability and tumor retention property, which increase the drug delivery efficiency and bioavailability. In vitro and in vivo research demonstrate the superior PDT efficiency of BSC by proteasome and Bcl-2 inhibitions. Of special note, the coordination-driven self-assembly of BSC is pH-responsive, which can be disassembled for controlled drug release upon tumor acidic microenvironment. This study will expand the applicability of self-delivery nanomedicine with sophisticated mechanisms for tumor treatment.

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The passage describes the development of a self-delivery biomedicine called BSC, which is designed to combat tumor cells' resistance to oxidative damage and apoptosis. BSC is formed through the self-assembly of three components: Bortezomib (BTZ), Sabutoclax (Sab), and Chlorin e6 (Ce6).

The interaction between BTZ and Sab promotes the assembly of a uniform ternary biomedicine through non-covalent intermolecular interactions. BTZ acts as a proteasome inhibitor, preventing tumor cells from scavenging damaged proteins and reducing their resistance to oxidative damage. Sab downregulates B-cell lymphoma 2 (Bcl-2), which decreases the levels of antiapoptotic proteins. The inhibition of both the proteasome and Bcl-2 increases cell apoptosis and enhances the efficacy of photodynamic therapy (PDT) performed by Ce6.

Remarkably, the carrier-free BSC possesses all the biological activities of its assembly elements, including photodynamic performance, proteasome inhibition, and Bcl-2 inhibition. Furthermore, BSC exhibits excellent cellular uptake ability and tumor retention properties, enhancing drug delivery efficiency and bioavailability. In vitro and in vivo studies demonstrate the superior efficacy of BSC in PDT through proteasome and Bcl-2 inhibitions.

One notable feature of BSC is its pH-responsive nature, as the coordination-driven self-assembly can be disassembled in the acidic microenvironment of tumors. This pH responsiveness enables controlled drug release within the tumor, enhancing the therapeutic effects.

Overall, this study introduces a self-delivery nanomedicine, BSC, which incorporates sophisticated mechanisms to address tumor resistance. The development of BSC expands the range of applications for self-delivery nanomedicine in tumor treatment.