Backgrounds: Surgical resection and adjunct chemotherapy or radio-therapy has been applied for the therapy of superficial malignant tumor in clinics. Whereas, there are still some problems limit its clinical use, such as severe pains and side effect. Thus, it is urgent need to develop effective, minimally invasive and low toxicity therapy stagey for superficial malignant tumor. Topical drug administration such as microneedle patches shows the advantages of reduced systemic toxicity and nimble application and, as a result, a great potential to treat superficial tumors. Methods: In this study, microneedle (MN) patches were fabricated to deliver photosensitizer IR820 and chemotherapy agent cisplatin (CDDP) for synergistic chemo-photodynamic therapy against breast cancer. Results: The MN could be completely inserted into the skin and the compounds carrying tips could be embedded within the target issue for locoregional cancer treatment. The photodynamic therapeutic effects can be precisely controlled and switched on and off on demand simply by adjusting laser. The used base material vinylpyrrolidone—vinyl acetate copolymer (PVPVA) is soluble in both ethanol and water, facilitating the load of both water-soluble and water-insoluble drugs. Conclusions: Thus, the developed MN patch offers an effective, user-friendly, controllable and low-toxicity option for patients requiring long-term and repeated cancer treatments.

Epigenetic regulation has emerged as a promising therapeutic strategy for lung cancer treatment, which can facilitate the antitumor responses by modulating epigenetic dysregulation of target proteins in lung cancer. The proteolysis-targeting chimera (PROTAC) reagent, dBET6 shows effective inhibition of bromodomain-containing protein 4 (BRD4) that exerts antitumor efficacy by degrading BRD4 via the ubiquitin-proteasome system. Nevertheless, the low tissue specificity and bioavailability impede its therapeutic effects and clinical translation on lung cancer treatment. Herein, we developed a type of dual targeting and bioresponsive nano-PROTAC (c R GD/L LC membrane/D S-P LGA/d B ET6, named RLDPB), which was constructed by using the pH and glutathione (GSH)-responsive polymer, disulfide bond-linked poly(lactic-co-glycolic acid) (PLGA-S-S-PLGA, DS-PLGA) to load the PROTAC agent dBET6, and further camouflaged with the homotypic LLC cell membranes, followed by the conjugation with cRGD ligand to the surface of the nanoparticles. Notably, RLDPB showed enhanced celluar uptake by lung cancer cells in vitro and accumulation in the tumors via the dual targeting structure including cRGD and LLC membrane. The pH/GSH responsiveness improved the release of dBET6 from the DS-PLGA-based nanoparticles within the cells. RLDPB was demonstrated to facilitate tumor regression by inducing the apoptosis of lung cancer cells with the degradation of BRD4. Thus, RLDPB can be considered a powerful tool to suppress lung cancer, which opens a new avenue to treat lung cancer by PROTAC.

Atherosclerosis is a major cause of death and disability in cardiovascular disease. Atherosclerosis associated with lipid accumulation and chronic inflammation leads to plaques formation in arterial walls and luminal stenosis in carotid arteries. Current approaches such as surgery or treatment with statins encounter big challenges in curing atherosclerosis plaque. The infiltration of proinflammatory M1 macrophages plays an essential role in the occurrence and development of atherosclerosis plaque. A recent study shows that TRIM24, an E3 ubiquitin ligase of a Trim family protein, acts as a valve to inhibit the polarization of anti-inflammatory M2 macrophages, and elimination of TRIM24 opens an avenue to achieve the M2 polarization. Proteolysis-targeting chimera (PROTAC) technology has emerged as a novel tool for the selective degradation of targeting proteins. But the low bioavailability and cell specificity of PROTAC reagents hinder their applications in treating atherosclerosis plaque. In this study we constructed a type of bioinspired PROTAC by coating the PROTAC degrader (dTRIM24)-loaded PLGA nanoparticles with M2 macrophage membrane (MELT) for atherosclerosis treatment. MELT was characterized by morphology, size, and stability. MELT displayed enhanced specificity to M1 macrophages as well as acidic-responsive release of dTRIM24. After intravenous administration, MELT showed significantly improved accumulation in atherosclerotic plaque of high fat and high cholesterol diet-fed atherosclerotic (ApoE^−/−) mice through binding to M1 macrophages and inducing effective and precise TRIM24 degradation, thus resulting in the polarization of M2 macrophages, which led to great reduction of plaque formation. These results suggest that MELT can be considered a potential therapeutic agent for targeting atherosclerotic plaque and alleviating atherosclerosis progression, providing an effective strategy for targeted atherosclerosis therapy.