Cancer, a global health burden, is characterized by uncontrolled cell growth and metastasis, often resulting in debilitating treatments and mortality. While conventional therapeutic strategies have improved survival rates, they are limited by challenges such as off-target toxicity and drug resistance. With their design to enable targeted drug delivery, nanoparticles have presented a promising avenue to overcome these limitations. Protein-based nanoparticles, particularly those based on albumin, are notable for their biocompatibility, stability, and ease of modification. The approval of Abraxane, an albumin-based nanoparticle formulation of paclitaxel, for metastatic breast cancer marked a significant milestone. However, further approvals have been slow to materialize until the recent approval of Fyarro® in 2021. This focused review highlights the potential of albumin-based nanoparticles, emphasizing their advantages, current state, and progress in clinical use as anticancer therapeutics. We also discuss challenges impeding new approvals and future directions for unlocking the full potential of this technology.

Chagas disease and leishmaniasis are two neglected tropical diseases that affect millions of people in low- and middle-income tropical countries. These diseases caused by protozoan parasites pose significant global health challenges, which have been exacerbated by the recent COVID-19 pandemic. There is an urgent need for novel therapeutics as current treatments are limited by toxicity and drug resistance. Nucleoside analogues, which have been extensively studied and successfully applied in antiviral and antitumor therapies, hold potential that has yet to be fully explored for treating these neglected diseases. In this review, we discuss the use of nucleoside analogues as promising therapeutic agents for Chagas disease and leishmaniasis. After briefly examining the pathology, progression, and current treatment options for these diseases, we provide a comprehensive analysis of the status of nucleoside analogues and explore their prospects. By outlining the current landscape and future directions, this review aims to guide research and development efforts towards more effective nucleoside-based treatments for Chagas disease and leishmaniasis.

Neglected tropical diseases (NTDs) remain a major global health challenge, particularly in low‐ and middle‐income countries. Kinetoplastid parasites causing Chagas disease, leishmaniasis, and African trypanosomiasis rely on host purine salvage pathways, making nucleoside analogues attractive therapeutic candidates. However, their clinical utility is limited by poor cellular uptake and rapid metabolism. Herein, we report the application of the ProTide prodrug technology, a clinically validated approach that enhances the intracellular delivery of nucleoside monophosphates for the treatment of kinetoplastids infections. As a proof of concept, a focused library of zidovudine (AZT) and cordycepin ProTide prodrugs was designed, synthesized, and evaluated for antiparasitic activity against T. b. rhodesiense , T. cruzi , and L. donovani , as well as for cytotoxicity in L6 rat myoblasts. Out of these, compound 16 exhibited substantial serum stability and potent activity (IC ₅₀ = 5 nM; selectivity index, SI = 2,560) against T. b. rhodesiense with robust activity also observed against T. cruzi and L. donovani. These findings establish the ProTide prodrug technology as a promising strategy for optimizing nucleoside analogues against kinetoplastid parasites and provide a framework for the development of new therapeutics for NTDs.

Background/Objectives: Curcumin (CUR) is a potent anticancer agent whose clinical application is hindered by its extremely poor aqueous solubility. This study reports the development of enzyme-responsive whey protein isolate (WPI) nanoparticles for CUR targeted delivery. Methods: To overcome the initial solubility barrier, CUR was first formulated as a solid dispersion with WPI using freeze-drying. This process resulted in a significant enhancement in aqueous solubility (up to 1478-fold), with CUR existing in molecular dispersion or in an amorphous state within the protein matrix as confirmed by Differential Scanning Calorimetry (DSC) and Fourier-transform infrared (FT-IR) spectroscopy. The solubilized CUR-WPI solid dispersion was subsequently used to generate nanoparticles via a thermal gelation method, avoiding the use of organic solvents or toxic chemical crosslinkers. Results: The resulting nanoparticles exhibited a high drug loading efficiency of 85%. In vitro release studies demonstrated minimal CUR release in physiological buffer (pH 7.4) over 24 h, whereas exposure to trypsin, a nonspecific serine protease used as an in vitro model for tumor-associated proteolytic activity, triggered rapid nanoparticle degradation and released 95% of CUR within 3 h. Conclusions: These findings suggest that WPI-based nanoparticles developed from solid dispersions offer a promising, biocompatible platform for the solubility enhancement and protease-triggered delivery of hydrophobic anticancer drugs.

Cancer, a global health burden, is characterized by uncontrolled cell growth and metastasis, often resulting in debilitating treatments and mortality. While conventional therapeutic strategies have improved survival rates, they are limited by challenges such as off-target toxicity and drug resistance. With their design to enable targeted drug delivery, nanoparticles have presented a promising avenue to overcome these limitations. Protein-based nanoparticles, particularly those based on albumin, are notable for their biocompatibility, stability, and ease of modification. The approval of Abraxane, an albumin-based nanoparticle formulation of paclitaxel, for metastatic breast cancer marked a significant milestone. However, further approvals have been slow to materialize until the recent approval of Fyarro® in 2021. This mini-review highlights the potential of albumin-based nanoparticles, focusing on their advantages, their current state, and progress in clinical use as anticancer therapeutics. We also discuss challenges impeding new approvals and future directions for unlocking the full potential of this technology.

L-Lactate is elevated in various disease states, and monitoring is important to the food industry and to the performance management of high-endurance athletes. Commercial monitors are enzyme-based with low upper limits of detection (<50 mM) and are less robust than synthetic sensors using L-lactate binding to boronic acid (BA). The fluorescence indicator displacement assay (FIDA) for lactate has not been investigated and is convenient since BA is known to bind to catechol dyes, including Alizarin Red S (ARS) with large increases in fluorescence intensity. Herein, reversible addition-fragmentation chain transfer (RAFT) dispersion PISA of N-phenylacrylamide (PhA) in water/ethanol using BA-containing polyacrylamide macroRAFT gave stable spherical core-shell nanoparticles (NPs) functionalized with BA at the surface. It is demonstrated that the degree of polymerization (DP) of the BA-containing block of NPs can be acquired from the fluorescence-derived binding constant (K_ARS) using the Benesi-Hildebrand approach. FIDA involved the displacement of ARS by the L-lactate quencher from the fluorescent NP complex and allows the detection of higher L-lactate concentrations (4.0-625 mM) than current commercial monitors. The derived Stern-Volmer constant (K_sv) is independent of DP of the BA-containing block and increased by ∼2.5 times by addition of ethanol to the pH 7.4 aqueous dispersion. When using D-glucose and D-fructose as quenchers, K_sv is about 4-fold smaller and 13-fold greater, respectively, than L-lactate.