Background: Amphotericin B (AmB) as a liposomal formulation of AmBisome is the first line of treatment for the disease, visceral leishmaniasis, caused by the parasite Leishmania donovani. However, nephrotoxicity is very common due to poor water solubility and aggregation of AmB. This study aimed to develop a water-soluble covalent conjugate of gold nanoparticle (GNP) with AmB for improved antileishmanial efficacy and reduced cytotoxicity. Methods: Citrate-reduced GNPs (∼39 nm) were functionalized with lipoic acid (LA), and the product GNP-LA (GL ∼46 nm) was covalently conjugated with AmB using carboxyl-to-amine coupling chemistry to produce GNP-LA-AmB (GL-AmB ∼48 nm). The nanoparticles were characterized by dynamic light scattering, transmission electron microscopy (TEM), and spectroscopic (ultraviolet–visible and infrared) methods. Experiments on AmB uptake of macrophages, ergosterol depletion of drug-treated parasites, cytokine ELISA, fluorescence anisotropy, flow cytometry, and gene expression studies established efficacy of GL-AmB over standard AmB. Results: Infrared spectroscopy confirmed the presence of a covalent amide bond in the conjugate. TEM images showed uniform size with smooth surfaces of GL-AmB nanoparticles. Efficiency of AmB conjugation was ∼78%. Incubation in serum for 72 h showed <7% AmB release, indicating high stability of conjugate GL-AmB. GL-AmB with AmB equivalents showed ∼5-fold enhanced antileishmanial activity compared with AmB against parasite-infected macrophages ex vivo. Macrophages treated with GL-AmB showed increased immunostimulatory T_h1 (IL-12 and interferon-γ) response compared with standard AmB. In parallel, AmB uptake was ∼5.5 and ∼3.7-fold higher for GL-AmB-treated (P<0.001) macrophages within 1 and 2 h of treatment, respectively. The ergosterol content in GL-AmB-treated parasites was ∼2-fold reduced compared with AmB-treated parasites. Moreover, GL-AmB was significantly less cytotoxic and hemolytic than AmB (P<0.01). Conclusion: GNP-based delivery of AmB can be a better, cheaper, and safer alternative than available AmB formulations.

The recent development of nanotechnology-based formulations improved the diagnostics and therapies for various diseases including cancer where lack of specificity, high cytotoxicity with various side effects, poor biocompatibility, and increasing cases of multi-drug resistance are the major limitations of existing chemotherapy. Nanoparticle-based drug delivery enhances the stability and bioavailability of many drugs, thereby increasing tissue penetration and targeted delivery with improved efficacy against the tumour cells. Easy surface functionalization and encapsulation properties allow various antigens and tumour cell lysates to be delivered in the form of nanovaccines with improved immune response. The nanoparticles (NPs) due to their smaller size and associated optical, physical, and mechanical properties have evolved as biosensors with high sensitivity and specificity for the detection of various markers including nucleic acids, protein/antigens, small metabolites, etc. This review gives, initially, a concise update on drug delivery using different nanoscale platforms like liposomes, dendrimers, polymeric & various metallic NPs, hydrogels, microneedles, nanofibres, nanoemulsions, etc. Drug delivery with recent technologies like quantum dots (QDs), carbon nanotubes (CNTs), protein, and upconverting NPs was updated, thereafter. We also summarized the recent progress in vaccination strategy, immunotherapy involving immune checkpoint inhibitors, and biomarker detection for various cancers based on nanoplatforms. At last, we gave a detailed picture of the current nanomedicines in clinical trials and their possible success along with the existing approved ones. In short, this review provides an updated complete landscape of applications of wide NP-based drug delivery, vaccinations, immunotherapy, biomarker detection & imaging for various cancers with a predicted future of nanomedicines that are in clinical trials. Graphical abstract

The study of tropical diseases like leishmaniasis, a parasitic disease, has not received much attention even though it is the second-largest infectious disease after malaria. As per the WHO report, a total of 0.7-1.0 million new leishmaniasis cases, which are spread by 23 Leishmania species in more than 98 countries, are estimated with an alarming 26,000-65,000 death toll every year. Lack of potential vaccines along with the cost and toxicity of amphotericin B (AmB), the most common drug for the treatment of leishmaniasis, has raised the interest significantly for new formulations and drug delivery systems including nanoparticle-based delivery as anti-leishmanial agents. The size, shape, and high surface area to volume ratio of different NPs make them ideal for many biological applications. The delivery of drugs through liposome, polymeric, and solid-lipid NPs provides the advantage of high biocomatibilty of the carrier with reduced toxicity. Importantly, NP-based delivery has shown improved efficacy due to targeted delivery of the payload and synergistic action of NP and payload on the target. This review analyses the advantage of NP-based delivery over standard chemotherapy and natural product-based delivery system. The role of different physicochemical properties of a nanoscale delivery system is discussed. Further, different ways of nanoformulation delivery ranging from liposome, niosomes, polymeric, metallic, solid-lipid NPs were updated along with the possible mechanisms of action against the parasite. The status of current nano-vaccines and the future potential of NP-based vaccine are elaborated here.