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Even the potential of T cell-mimicking nanotrap for long term viral control due to its overcoming of human immunodeficiency virus (HIV) genetic diversity and viral resistance, the robust HIV inhibition was not expected because these nanotraps displayed no obvious advantages compared with the infinite host cells. Herein, a glycoprotein 120 (gp120)-targeting polypeptide UM15 reinforced lymphocyte-mimicking nanotrap was constructed, and its improved HIV-1 inhibiting efficacy was validated. According to the results, the constructed nanotraps exhibited evident escaping ability from uptake of the mononuclear phagocyte system and highly improved binding ability with gp120 proteins. The constructed nanotraps neutralized all tested HIV-1 pseudo typed viruses with IC80 of 21.0 µg/mL, and inhibited both X4-tropic and R5-tropic HIV-1 with IC80 of 34.4 and 20.6 µg/mL, respectively. Approximately 40% of gp120 was observed to be shed from pseudo virus, and above 40% bystander T cells were prevented from gp120-induced death by the constructed nanotraps. The safety of the constructed nanotraps was confirmed both in vitro and in mice. Therefore, the constructed nanotraps could specifically neutralize free HIV-1, selectively bind with gp120 expressing HIV-1 infected cells, cause gp120 shedding, inhibit gp120-induced bystander T cell killing on the premise of safety, and were considered as promising therapeutic agents for precise inhibition of HIV. [ABSTRACT FROM AUTHOR]

Despite the success of small interfering RNA (siRNA) in clinical settings and its potential value in human immunodeficiency virus (HIV) therapy, the rapid clearance and absence of precise delivery to target cells still hinder the therapeutic effect of siRNA. Herein, a new system, which can escape immune recognition, has HIV‐1 neutralizing capacity, and the ability to deliver siRNA specifically into HIV‐1‐infected cells, is constructed by functionalizing siRNA delivery lipid nanoparticles with the lymphocyte membrane and 12p1. The constructed system is shown to escape uptake by the mononuclear phagocyte system. The constructed system exhibits strong binding ability with gp120, thus displaying distinguished neutralizing breadth and potency. The constructed system neutralizes all tested HIV‐1 pseudotyped viruses with a geometric mean 80% inhibitory concentration (IC80) of 29.75 µg mL−1 and inhibits X4‐tropic HIV‐1 with an IC80 of 64.20 µg mL−1, and R5‐tropic HIV‐1 with an IC80 of 16.39 µg mL−1. The new system also specifically delivers siRNA into the cytoplasm of HIV‐1‐infected cells and exhibits evident gene silencing of tat and rev. Therefore, this new system can neutralize HIV‐1 and deliver siRNA selectively into HIV‐1‐infected cells and may be a promising therapeutic candidate for the precise therapy of HIV. [ABSTRACT FROM AUTHOR]

As one of the most frequent complications of critical illness, acute lung injury (ALI) carries a high risk of clinical morbidity and mortality. Cepharanthine (CPA) has significant anti-inflammatory activity, however, due to poor water solubility, low bioavailability, and short half-life, it fails to provide effective clinical management measures. Here, we explored the flexibility of an erythrocyte-anchoring strategy using CPA-encapsulated chitosan-coating nanoparticles (CPA-CNPs) anchored onto circulating erythrocytes for the treatment of ALI. CPA-CNPs adhered to erythrocytes successfully (E-CPA-CNPs) and exhibited high erythrocyte adhesion efficiency (>80%). Limited toxicity and favorable biocompatibility enabled further application of E-CPA-CNPs. Next, the reticuloendothelial system evasion features were analyzed in RAW264.7 macrophages and Sprague-Dawley rats. Compared with bare CPA-CNPs, erythrocyte-anchored CNPs significantly decreased cellular uptake in immune cells and prolonged circulation time in vivo. Notably, the erythrocyte-anchoring strategy enabled CNPs to be delivered and accumulated in the lungs (up to 6-fold). In the ALI mouse model, E-CPA-CNPs attenuated the progression of ALI by inhibiting inflammatory responses. Overall, our results demonstrate the outstanding advantages of erythrocyte-anchored CPA-CNPs in improving the pharmacokinetics and bioavailability of CPA, which offers great promise for a lung-targeted drug delivery system for the effective treatment of ALI. [ABSTRACT FROM AUTHOR]