Surface‐Functionalized Carrier‐Free Drug Nanorods for Leukemia

Abstract

Pure drug nanoparticles have emerged as an alternate method for formulating extremely hydrophobic drugs. Herein, a simple and efficient process for synthesizing PEGylated and antibody-conjugated, carrier-free nanomedicine is reported as a promising strategy to deliver the drug, Camptothecin (CPT) for aggressive circulating tumors such as Acute Myeloid Leukemia (AML). Size, shape, and surface morphology of pure drug nanorods (NRs) are examined and characterized by a variety of techniques. Incorporation of polyethylene glycol (PEG) onto the particle changed its surface charge and topography while affecting its drug-dissolution kinetics. Furthermore, the toxicity of PEGylated versus non-PEGylated forms of humanized anti-CD33 antibody (Hu195Ab)-coated CPT NRs are compared. Hu195Ab drug-linked NRs increased cell killing in leukemic cells and surface PEGylation show reduced non-specific uptake in cells. The results demonstrate that surface-modified carrier-free nanodrugs could have significant implications in cancer drug delivery for treating AML. This would be the first instance of studying the potential of surface-functionalized carrier-free drug NRs in the treatment of leukemia.

Nanocrystals: A perspective on translational research and clinical studies

“…The internalized positively charged nanocrystals further interact with the negatively charged organelles and DNA . A similar observation was also noted for paclitaxel nanocrystals where a positive charge led to higher cell uptake and cytotoxicity compared to negatively charged particles . On the contrary, negatively charged nanocrystals exhibited significant uptake via clathrin‐ and caveolae‐mediated uptake mechanisms .…”

“…4 It has also been shown that surface modifications can significantly affect the dissolution kinetics of pure drug NPs. [66][67][68][69] Stiffness and surface texture are also known impact the in vivo performance of NPs. 62 components crucial to the successful integration or rejection of these materials.…”

“…82 A similar observation was also noted for paclitaxel nanocrystals where a positive charge led to higher cell uptake and cytotoxicity compared to negatively charged particles. 66 On the contrary, negatively charged nanocrystals exhibited significant uptake via clathrin-and caveolaemediated uptake mechanisms. 83 Additionally, excessive positive and negative surface charges on NPs have been shown to induce higher rates of opsonization and capture by the immune cells in vivo.…”

“…Sonvico et al showed that dextran coatings on maghemite NPs can achieve comparable disaggregation properties to PEG coatings and can be used to conjugate targeting moieties . It has also been shown that surface modifications can significantly affect the dissolution kinetics of pure drug NPs . Stiffness and surface texture are also known impact the in vivo performance of NPs .…”

Materials for Immunotherapy

“…It was demonstrated that, compared to spherical nanoparticles of the same volume, nanoellipsoids with MHC‐Ig and anti‐CD28 conjugated to their surfaces enhanced antigen‐specific CTL proliferation and improved pharmacokinetic properties in vivo by evading cellular uptake by macrophages. Recently, Mitragotri and co‐workers developed nanoellipsoids made exclusively from drugs for acute myeloid leukemia treatment . The pure drug nanoellipsoids were synthesized by self‐assembly of a highly hydrophobic drug (camptothecin), followed by surface decoration of PEG and humanized anti‐CD33.…”