@article{cheng_henick_cheng_2024, title={Anticancer Therapy Targeting Cancer-Derived Extracellular Vesicles}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.3c06462}, journal={ACS NANO}, author={Cheng, Xiao and Henick, Brian S. and Cheng, Ke}, year={2024}, month={Feb} } @article{cheng_hu_cheng_2023, title={Microneedle Patch Delivery of PROTACs for Anti-Cancer Therapy}, volume={6}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.3c03166}, abstractNote={Proteolysis-targeting chimera (PROTAC) is an emerging technique for degrading disease-related proteins. However, the current PROTACs suffer from inadequate solubility and lack of organ targeting, which has hampered their druggability. Herein, we report direct and sustained delivery of PROTACs using microneedle patches to the diseased tissues. In this study, we use an estrogen receptor alpha (ERα)-degrading PROTAC, ERD308, to treat ER-positive breast cancer. A pH-sensitive micelle, MPEG-poly(β-amino ester) (MPEG-PAE), is used to encapsulate ERD308 along with an FDA-approved CDK4/6 inhibitor, Palbociclib (Pal), before loading into biodegradable microneedle patches. These patches enable prolonged drug release into deep tumors, maintaining therapeutic levels for at least 4 days, with an excellent drug retention rate of over 87% in tumors. ERD308 released from the microneedle patches can sufficiently degrade ERα in MCF7 cells. Co-administration of ERD308 and Palbociclib exhibits excellent efficacy by over 80% tumor reduction as well as a good safety profile. Our work demonstrates the feasibility and proof-of-concept therapeutic potential of using microneedle patches to directly deliver PROTACs into tumors.}, journal={ACS NANO}, author={Cheng, Xiao and Hu, Shiqi and Cheng, Ke}, year={2023}, month={Jun} } @article{shi_cheng_cheng_2022, title={Gecko-Inspired Adhesives with Asymmetrically Tilting-Oriented Micropillars}, volume={38}, ISSN={["0743-7463"]}, DOI={10.1021/acs.langmuir.2c01002}, abstractNote={The anisotropic adhesion behavior of the gecko is closely related to their feet and is comprised of keratinous hairs, setae, where van der Waals forces permit attachment and detachment during locomotion. Previous research either achieved only isotropic adhesion behaviors or involved the complicated photolithography method. Here, we reported a simple way to achieve the anisotropic adhesion behaviors of gecko-inspired adhesives, consisting of micropillars with asymmetrically tilted orientation via the 3D printing technique. The adhesive forces of structured polymer pillars achieved 4-fold stronger, compared to controls with the plain surface. The anisotropic adhesion behavior is presented on the patterned surface and is two times stronger along the gripping direction compared to the releasing direction on the adhesives, which is attributed to the asymmetric stress distributions at the edges, as well as the stresses resulting from the moment with the sheared top. The finite element analysis is applied to demonstrate the stress distributions and displacement variations. This work provides the insight into the design and fabrication of gecko-inspired adhesives with anisotropic adhesion behaviors in practical applications.}, number={29}, journal={LANGMUIR}, author={Shi, Weiwei and Cheng, Xiao and Cheng, Ke}, year={2022}, month={Jul} } @article{popowski_moatti_scull_silkstone_lutz_lópez de juan abad_george_belcher_zhu_mei_et al._2022, title={Inhalable dry powder mRNA vaccines based on extracellular vesicles}, volume={5}, ISSN={2590-2385}, url={http://dx.doi.org/10.1016/j.matt.2022.06.012}, DOI={10.1016/j.matt.2022.06.012}, abstractNote={Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung-derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nanoparticle liposomes (Lipos), Lung-Exos exhibited superior distribution to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature storage for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.}, number={9}, journal={Matter}, publisher={Elsevier BV}, author={Popowski, Kristen D. and Moatti, Adele and Scull, Grant and Silkstone, Dylan and Lutz, Halle and López de Juan Abad, Blanca and George, Arianna and Belcher, Elizabeth and Zhu, Dashuai and Mei, Xuan and et al.}, year={2022}, month={Sep}, pages={2960–2974} } @article{xie_li_zhang_zhu_mei_wang_cheng_li_wang_cheng_2021, title={A trifunctional contraceptive gel enhances the safety and quality of sexual intercourse}, volume={6}, ISSN={["2452-199X"]}, url={https://doi.org/10.1016/j.bioactmat.2020.11.031}, DOI={10.1016/j.bioactmat.2020.11.031}, abstractNote={Current contraceptive methods come with a number of drawbacks, including low efficacy, in the case of commercial contraceptive gels, and a reduction in the quality of sexual intercourse, in the case of condoms. Adding pharmacologically-active agents to contraceptive gels holds the potential to improve sexual experience, and hardbor safety and hygiene. In this study, we fabricated a carbomer-based contraceptive gel consisting of three agents: tenofovir, gossypol acetate, and nitroglycerin (TGN), with pH adjusted to 4.5 (to be compatible with the vagina). In vitro, the gossypol component of the contraceptive gel proved to be an effective spermicide. When the concentration of gossypol acetate was 10 mg/ml, the spermicidal ability reached 100% after 30 s. In addition, tenofovir in the gel significantly inhibited lentiviral transfection efficiency in cell-containing media. In 6 pairs of rats, the gel successfully prevented all females from conceiving after successful mating. Moreover, increased sexual frequency and enhanced erection, which were promoted by the nitroglycerin in the components, were observed in male rats that had the gel applied to their penises. This novel TGN contraceptive gel yielded a higher contraceptive success rate than that of the commercial contraceptive gel (Contragel®). In addition, it has the added benefits to prevent sexually transmitted diseases and improve male libido and erectile function during sexual intercourse. Combining three FDA-approved and marketed agents together, our trifunctional TGN gel has a great potential for further translation and commercialization.}, number={6}, journal={BIOACTIVE MATERIALS}, publisher={Elsevier BV}, author={Xie, Mengjie and Li, Junlang and Zhang, Sichen and Zhu, Dashuai and Mei, Xuan and Wang, Zhenzhen and Cheng, Xiao and Li, Zhenhua and Wang, Shaowei and Cheng, Ke}, year={2021}, month={Jun}, pages={1777–1788} } @article{hu_wang_li_zhu_cores_wang_li_mei_cheng_su_et al._2021, title={Platelet membrane and stem cell exosome hybrids enhance cellular uptake and targeting to heart injury}, volume={39}, ISSN={["1878-044X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85107566346&partnerID=MN8TOARS}, DOI={10.1016/j.nantod.2021.101210}, abstractNote={Exosomes from mesenchymal stem cells have been largely studied as therapeutics to treat myocardial infarctions. However, exosomes injected for therapeutic purposes face a number of challenges, including competition from exosomes already in circulation, and the internalization/clearance by the mononuclear phagocyte system. In this study, we hybrid exosomes with platelet membranes to enhance their ability to target the injured heart and avoid being captured by macrophages. Furthermore, we found that encapsulation by the platelet membranes induces macropinocytosis, enhancing the cellular uptake of exosomes by endothelial cells and cardiomyocytes strikingly. In vivo studies showed that the cardiac targeting ability of hybrid exosomes in a mice model with myocardial infarction injury. Last, we tested cardiac functions and performed immunohistochemistry to confirm a better therapeutic effect of platelet membrane modified exosomes compared to non-modified exosomes. Our studies provide proof-of-concept data and a universal approach to enhance the binding and accumulation of exosomes in injured tissues.}, journal={NANO TODAY}, author={Hu, Shiqi and Wang, Xianyun and Li, Zhenhua and Zhu, Dashuai and Cores, Jhon and Wang, Zhenzhen and Li, Junlang and Mei, Xuan and Cheng, Xiao and Su, Teng and et al.}, year={2021}, month={Aug} } @misc{cheng_cheng_2021, title={Visualizing cancer extravasation: from mechanistic studies to drug development}, volume={40}, ISSN={["1573-7233"]}, DOI={10.1007/s10555-020-09942-2}, abstractNote={Metastasis is a multistep process that accounts for the majority of cancer-related death. By the end of metastasize dissemination, circulating tumor cells (CTC) need to extravasate the blood vessels at metastatic sites to form new colonization. Although cancer cell extravasation is a crucial step in cancer metastasis, it has not been successfully targeted by current anti-metastasis strategies due to the lack of a thorough understanding of the molecular mechanisms that regulate this process. This review focuses on recent progress in cancer extravasation visualization techniques, including the development of both in vitro and in vivo cancer extravasation models, that shed light on the underlying mechanisms. Specifically, multiple cancer extravasation stages, such as the adhesion to the endothelium and transendothelial migration, are successfully probed using these technologies. Moreover, the roles of different cell adhesive molecules, chemokines, and growth factors, as well as the mechanical factors in these stages are well illustrated. Deeper understandings of cancer extravasation mechanisms offer us new opportunities to escalate the discovery of anti-extravasation drugs and therapies and improve the prognosis of cancer patients.}, number={1}, journal={CANCER AND METASTASIS REVIEWS}, author={Cheng, Xiao and Cheng, Ke}, year={2021}, month={Mar}, pages={71–88} }