Nanoengineering a Zeolitic Imidazolate Framework-8 Capable of Manipulating Energy Metabolism against Cancer Chemo-Phototherapy Resistance.

Chemo-phototherapy has emerged as a promising approach to complement traditional cancer treatment and enhance therapeutic effects. However, it still faces the challenges of drug efflux transporter-mediated chemoresistance and heat shock proteins (HSPs)-mediated phototherapy tolerance, which both depend on an excessive supply of adenosine triphosphate. Therefore, manipulating energy metabolism to impair the expression or function of P-glycoprotein (P-gp) and HSPs may be a prospective strategy to reverse cancer therapeutic resistance. Herein, a chondroitin sulfate (CS)-functionalized zeolitic imidazolate framework-8 (ZIF-8) chemo-phototherapy nanoplatform (CS/ZIF-8@A780/DOX NPs) is rationally designed that is capable of manipulating energy metabolism against cancer therapeutic resistance by integrating the photosensitizer IR780 iodide (IR780)-conjugated atovaquone (ATO) (A780) and the chemotherapeutic agent doxorubicin (DOX). Mechanistically, ATO and zinc ions that are released in the acidic tumor microenvironment can lead to systematic energy exhaustion through disturbing mitochondrial electron transport and the glycolysis process, thus suppressing the activity of P-gp and HSP70, respectively. In addition, CS is used on the surface of ZIF-8@A780/DOX NPs to improve the targeting capability to tumor tissues. These data provide an efficient strategy for manipulating energy metabolism for cancer treatment, especially for overcoming cancer chemo-phototherapy resistance.

Engineered Bifunctional Proteins for Targeted Cancer Therapy: Prospects and Challenges.

Bifunctional proteins (BFPs) are a class of therapeutic agents produced through genetic engineering and protein engineering, and are increasingly used to treat various human diseases, including cancer. These proteins usually have two or more biological functions-specifically recognizing different molecular targets to regulate the related signaling pathways, or mediating effector molecules/cells to kill tumor cells. Unlike conventional small-molecule or single-target drugs, BFPs possess stronger biological activity but lower systemic toxicity. Hence, BFPs are considered to offer many benefits for the treatment of heterogeneous tumors. In this review, the authors briefly describe the unique structural feature of BFP molecules and innovatively divide them into bispecific antibodies, cytokine-based BFPs (immunocytokines), and protein toxin-based BFPs (immunotoxins) according to their mode of action. In addition, the latest advances in the development of BFPs are discussed and the potential limitations or problems in clinical applications are outlined. Taken together, future studies need to be centered on understanding the characteristics of BFPs for optimizing and designing more effective such drugs.

Sugarcane bagasse lignin, and silica gel and magneto-silica as drug vehicles for development of innocuous methotrexate drug against rheumatoid arthritis disease in albino rats.

The present study clarifies co-therapy action of deliveries from their textural changes point of view. Methotrexate (MTX) was immobilized onto biodegradable lignin, silica gel and iron/silica nanocomposite. Loaded-MTX was i.p. injected into albino rats at doses of 0.25 and 0.5mg/kg/week for 2.5months, after which spleen, liver, testes and knee joint tissues were collected for tests. IFN-γ and IL-17A mRNA gene expressions in spleen in all biological samples were determined by RT-PCR. Physicochemical features of drug carriers were monitored by XRD, BET-PSD, SEM and TEM. Drug inflammatory-site targeting was found to be closely related to the physico-features of deliverers. The interlayered lignin of micro- and meso-pore channels directed MTX toward concealed infected cells in liver and testes tissues, while meso-structured silica flacks satisfied by gathering MTX around knee joints. The magneto-silica nanocomposite targeted MTX toward spleen tissue, which is considered as a lively factory for the production of electron rich compounds.