Inactivation of HIV-1 Infection through Integrative Blocking with Amino Phenylboronic Acid Attributed Carbon Dots
ACS BIOMATERIALS SCIENCE & ENGINEERING
Authors: Aung, Yu Yu; Kristanti, Alfinda Novi; Khairunisa, Siti Qamariyah; Nasronudin, Nasronudin; Fahmi, Mochamad Zakki
Abstract
Current antiretroviral HIV therapies continue to have problems related to procedural complications, toxicity, and uncontrolled side effects. In this study, amino phenylboronic acid-modified carbon dots (APBA-CDs) were introduced as a new nanoparticle-based on gp120 targeting that inhibits HIV-1 entry processes. Prolonged by simple pyrolysis for preparing carbon dots, this report further explores attributing amino phenylboronic acid on carbon dots, which prove the formation of graphene-like structures on carbon dots and boronic acid sites, thereby enabling the enhancement of positive optical properties through photoluminescent detection. Aside from performing well in terms of biocompatibility and low cytotoxicity (the CC50 reach up to 11.2 mg/mL), APBA-CDs exhibited superior capabilities in terms of prohibiting HIV-1 entry onto targeted MOLT-4 cells recognized by the delimitations of syncitia formation and higher ATP signal rather than bare carbon dots. The modified carbon dots also promote dual-action on HIV-1 treatment by both intracellularly and extracellularly viral blocking by combining with the Duviral drug, along with compressing p24 antigen signals that are better than APBA-CDs and Duviral itself.
Preclinical Safety Evaluation of HIV-1 gp120 Responsive Microbicide Delivery System in C57BL/6 Female Mice
MOLECULAR PHARMACEUTICS
Authors: Coulibaly, Fohona S.; Ezoulin, Miezan J. M.; Dim, Daniel C.; Molteni, Agostino; Youan, Bi-Botti C.
Abstract
Many novel vaginal/rectal microbicide formulations failed clinically due to safety concerns, indicating the need for the early investigation of lead microbicide formulations. In this study, the preclinical safety of an HIV-1 gp120 and mannose responsive microbicide delivery system (MRP) is evaluated in C57BL/6 mice. MRP was engineered through the layer-by-layer coating of calcium carbonate (CaCO3) with Canavalia ensiformis lectin (Con A) and glycogen. MRP mean particle diameter and zeta potential were 857.8 +/- 93.1 nm and 2.37 +/- 4.12 mV, respectively. Tenofovir (TFV) encapsulation and loading efficiencies in MRP were 70.1% and 16.3% w/w, respectively. When exposed to HIV-1 rgp120 (25 mu g/mL), MRP released a significant amount of TFV (similar to 5-fold higher) in vaginal and seminal fluid mixture compared to the control (pre-exposure) level (similar to 59 mu g/mL) in vaginal fluid alone. Unlike the positive control treated groups (e.g., nonoxynol-9), no significant histological damages and CD45+ cells infiltration were observed in the vaginal and major reproductive organ epithelial layers. This was probably due to MRP biocompatibility and its isosmolality (304.33 +/- 0.58 mOsm/kg). Furthermore, compared to negative controls, there was no statistically significant increase in pro-inflammatory cytokines such as IL1 alpha, Il beta, IL7, IP10, and TNF alpha. Collectively, these data suggest that MRP is a relatively safe nanotemplate for HIV-1 gp120 stimuli responsive vaginal microbicide delivery system.