CD4+ T cell-targeting immunoliposomes for treatment of latent HIV reservoir.

Active targeting nano-delivery is a promising approach to enhance therapeutic efficacy and specificity to the target cells. Liposomes (LPs) have been widely studied for the active targeting delivery due to their low toxicity, biodegradability, biocompatibility, and feasibility of surface medication to provide the interactions with cell receptors. One of the strategies is to functionalize the surface of LPs with monoclonal antibodies (mAbs) to obtain immunoliposomes (imLPs) that recognize specific receptors on target cells. Among several target cells, CD4+ T cells are known for playing a pivotal role in controlling the immune system in several diseases, including cancers, inflammatory diseases, and viral infections, particularly HIV-1. Here, we demonstrate two methods for conjugating αCD4 mAb with imLPs for specific targeting of CD4+ T cells that can harbor viral genome and serve as a predominant latent HIV reservoir. LPs conjugated with αCD4 mAb via neutravidin-biotin linkage were used for selectively targeting CD4+ J-Lat 10.6 cells. We demonstrate, via flow cytometry, the importance of the conjugation step, mAb density, and the presence of polyethylene glycol (PEG) for effective drug delivery to CD4+ T cells. The cellular uptake of imLPs is substantially higher if the imLPs are functionalized with the pre-conjugated αCD4 mAb-neutravidin complex. Furthermore, imLPs loaded with HIV-1 latency reversing agent, suberoylanilide hydroxamic acid (SAHA), could reactivate the J-Lat 10.6 cells, suggesting that the αCD4-imLPs could be potentially used as a targeted drug delivery system for HIV-1 latency reactivation or other CD4-targeted immunotherapies.

Silk Fibroin-Coated Liposomes as Biomimetic Nanocarrier for Long-Term Release Delivery System in Cancer Therapy.

Despite much progress in cancer therapy, conventional chemotherapy can cause poor biodistribution and adverse side-effects on healthy cells. Currently, various strategies are being developed for an effective chemotherapy delivery system. Silk fibroin (SF) is a natural protein used in a wide range of biomedical applications including cancer therapy due to its biocompatibility, biodegradability, and unique mechanical properties. In this study, SF-coated liposomes (SF-LPs) were prepared as a biomimetic drug carrier. Physicochemical properties of SF-LPs were characterized by Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering, zeta potential measurement, and transmission electron microscopy (TEM). In vitro release of SF-LPs loaded with doxorubicin (DOX-SF-LPs) was evaluated over 21 days. Anticancer activity of DOX-SF-LPs was determined against MCF-7 and MDA-MB231 cells using the MTT assay. SF-LPs containing 1% SF exhibited favorable characteristics as a drug carrier. SF coating modified the kinetics of drug release and reduced the cytotoxic effect against L929 fibroblasts as compared to the uncoated liposomes containing cationic lipid. DOX-SF-LPs showed anticancer activity against breast cancer cells after 48 h or 72 h at 20 µM of DOX. This approach provides a potential platform of long-term release that combines biocompatible SF and phospholipids for cancer therapy, achieving efficient drug delivery and reducing side-effects.

Drug Delivery System Targeting CD4+ T Cells for HIV-1 Latency Reactivation Towards the Viral Eradication.

Development of a cure for HIV/AIDS has been a great challenge due to the establishment of the HIV-1 viral reservoir, mainly within resting CD4+ memory T cells. As a step towards a cure for HIV, this study aimed to develop an approach that reactivates HIV-1 latently infected cells by employing a drug delivery system using immunoliposomes targeting CD4+ T cells. The immunoliposomes were examined for physicochemical properties and determined for their potential stability. A histone deacetylase (HDAC) inhibitor SAHA was used as a model drug being encapsulated within the immunoliposomes that are conjugated with anti-CD4 antibodies. The immunoliposomes are effectively and specifically taken up by the CD4+ J-Lat 10.6 cells, and significantly less so by the CD4- ACH-2 cells. For HIV-1 latent cell reactivation, SAHA-encapsulated immunoliposomes (SAHA-IL) and SAHA-encapsulated liposomes (SAHA-LP) can reactivate HIV latency as effectively as SAHA compound alone. Additionally, a combination of SAHA-IL and a protein kinase C activator, bryostatin-1, also exhibits a synergistic effect on the reactivation. The developed system thus presents a viable option to become a promising approach for HIV-1 latency reversing treatment, a strategy towards developing a functional cure for HIV.