ACS Nano2021ReviewDrug Delivery
Paula M. Cevaal, Abdalla Ali, Ewa Czuba-Wojnilowicz, Jori Symons, Sharon R. Lewin, Christina Cortez-Jugo, Frank Caruso
T cells are attractive targets for immunotherapy, cancer, HIV, autoimmunity, and inflammation, but nanoparticle delivery to T cells remains a major technological challenge due to their nonphagocytic nature and multiple physiological barriers. There is a need for rational design principles for in vivo T cell-targeting nanoparticles. --- - Barriers: Only ~2–3% of all T cells are in blood; <5% of administered nanoparticles typically reach target tissue; nanoparticles <~6 nm are renally cleared; T cells are nonphagocytic with low endocytosis rates; slow endosomal acidification in primary T cells can reduce pH-dependent cargo release. - Size rules: For receptor-mediated endocytosis (RME), optimum nanoparticle diameter ~50 nm; <200 nm preferred; >10 nm needed to avoid renal clearance; 10–100 nm ideal for lymph node delivery; <100 nm promotes escape from mononuclear phagocyte system scavenging. - Targeting outcomes: CD3-targeted PBAE/polygluta
Read the article →Chemical Society Reviews2017ReviewNon-viral Gene Delivery
Shahed Behzadi, Vahid Serpooshan, Wei Tao, Majd A. Hamaly, Mahmoud Y. Alkawareek, Erik C. Dreaden, Dennis Brown, Alaaldin M. Alkilany, Omid C. Farokhzad, Morteza Mahmoudi
Nanoparticles (NPs) are increasingly used in consumer goods, electronics, and pharmaceuticals, but their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. While many NPs require safe entry into cells for therapeutic efficacy, efficient and controlled entry/trafficking remains a major challenge. A comprehensive understanding of NP cellular uptake and trafficking mechanisms is critical for designing efficient and safe nanomedicines. --- - Size: ~50 nm is the optimum size for highest cellular uptake in certain cells; larger particles (1000–2000 nm) show maximal phagocytic uptake; smaller NPs (2.1 nm) can enter the nucleus/nucleoli, while 4.4 nm NPs show reduced penetration. - Shape: Spherical NPs undergo higher cellular uptake than rod-shaped NPs; lower aspect ratio rods are taken up faster than higher aspect ratio rods; rod and disc NPs are taken up twice as quickly as spheres
Read the article →Pharmaceutical Research2011ReviewNon-viral Gene Delivery
Wei-Yun Sheng, Leaf Huang
The immune system can recognize and kill pre-cancer and cancer cells, but surviving tumor cells learn to escape immune surveillance after immunoselection. Cancer immunotherapy aims to overcome these escape mechanisms. Nanomedicine offers tools—nanodiagnostics and nanobiopharmaceuticals—to deliver antigens, adjuvants, cytokines, and nucleic acids, and to target immune cells or the tumor microenvironment, potentially improving the efficacy of cancer immunotherapy. --- - G3139-LNP (CpG ODN against Bcl-2 encapsulated in lipid nanoparticles): enhanced IFN-γ, IL-2, IL-4, and IL-10 by ~4-fold; significantly enlarged spleen; inhibited tumor growth by >50%; prolonged host survival by 245%. - IL-18 + liposomal doxorubicin combination: 22% of mice remained tumor-free for 6 months vs 0% for either monotherapy in an ID8 ovarian tumor model. - Sipuleucel-T (Provenge®): first FDA-approved cancer therapeutic vaccine (April 2010); in phase III, extended
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