Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid

Abstract

Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 < 5.0 μg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field.

Hyaluronic Acid-Coated Camptothecin Nanocrystals for Targeted Drug Delivery to Enhance Anticancer Efficacy

“…Undoubtedly, except for passive targeting (EPR effect) and cell targeting (CD44 binding), the HA-coated CPT nanocrystals are also able to partly target the organelle (mitochondria), which contributes to overall enhanced anticancer efficacy and high selectivity. 12 On the other side, for the control group, the majority of dyed normal mitochondria displayed basically uniform round structure, and they were plump and globular in shape, recorded 5−10 μm in diameter. When treated with free CPT or naked CPT nanocrystals, there was a slight variation in mitochondria morphology: a small portion of mitochondria became swollen or showed irregular shapes, demonstrating their relatively low mitochondria toxicity.…”

“…On the one side, from Figure a, we could observe the apparent co-localization of mitochondria and CPT in the HA-coated CPT nanocrystals treated group, indicating their mitochondria targeting capability. Undoubtedly, except for passive targeting (EPR effect) and cell targeting (CD44 binding), the HA-coated CPT nanocrystals are also able to partly target the organelle (mitochondria), which contributes to overall enhanced anticancer efficacy and high selectivity . On the other side, for the control group, the majority of dyed normal mitochondria displayed basically uniform round structure, and they were plump and globular in shape, recorded 5–10 μm in diameter.…”

“…Both HA-coated or naked CPT nanocrystals were prepared by a classic bottoms-up method: antisolvent precipitation augmented by intense sonication. , A DMSO solution (0.2 mL) of 5 mg/mL CPT was injected into 10 mL of HA solution (pH = 4) with different concentrations (0.25–1.00%, w/v). The mixture was subject to intense sonication at 200 W for 20 min, followed by constant stirring (500 rpm for 10 min, 300 rpm for 30 min, 100 rpm for several hours) at room temperature allowing for HA adsorption.…”

“…Although CPT nanocrystals demonstrated considerable advantages in the field of cancer treatment, their further clinical applications were still hampered. Since pure CPT nanocrystals lacked active targeting accuracy, they still displayed low bioavailability, limited therapeutic efficacy, and severe side effects. − Consequently, more elaborated active tumor targeting strategy, for example, based on the ligand and receptors overexpressed on surface of cancer cells, should be designed and adopted, to enhance the specific delivery and internalization of drugs by cancer cells. − …”

Self-Polymerization of Dopamine in Acidic Environments without Oxygen

“…An antisolvent precipitation augmented by sonication was used to produce CPT nanocrystals . In PDA coating, CPT nanocrystals were resuspended in 3 mL of freshly prepared PAW solution.…”