Bridging Smart Nanosystems with Clinically Relevant Models and Advanced Imaging for Precision Drug Delivery

Abstract

Intracellular delivery of nano‐drug‐carriers (NDC) to specific cells, diseased regions, or solid tumors has entered the era of precision medicine that requires systematic knowledge of nano‐biological interactions from multidisciplinary perspectives. To this end, this review first provides an overview of membrane‐disruption methods such as electroporation, sonoporation, photoporation, microfluidic delivery, and microinjection with the merits of high‐throughput and enhanced efficiency for in vitro NDC delivery. The impact of NDC characteristics including particle size, shape, charge, hydrophobicity, and elasticity on cellular uptake are elaborated and several types of NDC systems aiming for hierarchical targeting and delivery in vivo are reviewed. Emerging in vitro or ex vivo human/animal‐derived pathophysiological models are further explored and highly recommended for use in NDC studies since they might mimic in vivo delivery features and fill the translational gaps from animals to humans. The exploration of modern microscopy techniques for precise nanoparticle (NP) tracking at the cellular, organ, and organismal levels informs the tailored development of NDCs for in vivo application and clinical translation. Overall, the review integrates the latest insights into smart nanosystem engineering, physiological models, imaging‐based validation tools, all directed towards enhancing the precise and efficient intracellular delivery of NDCs.

Combination of PEGylation and Cationization on Phospholipid-Coated Cyclosporine Nanosuspensions for Enhanced Ocular Drug Delivery

“…NS@lipid-PEG/CKC (0.02%) with higher positive zeta potential showed higher cellular uptake by HCECs at 4 and 6 h (Figure A). According to the literature, the positively charged nanomedicine may be electrostatically attracted by the negatively charged cell membrane, leading to increased membrane fluidity and membrane wrapping. , Furthermore, the cellular uptake of the positively charged nanomedicine is predominantly through micropinocytosis, which might also be true for NS@lipid-PEG/CKC reported here, whereas the negatively charged nanomedicine is suggested to be taken up via clathrin-/caveolae-independent endocytosis. , The specific cellular uptake mechanism of NS@lipid-PEG/CKC will be explored in future research.…”

Mitochondria-Targeted Natural Antioxidant Nanosystem for Diabetic Vascular Calcification Therapy

“…However, T4O has a low bioavailability due to its low solubility and stability when exposed to light, heat, moisture, and oxygen. Nanodrug delivery systems have made tremendous contributions to improve the bioavailability of drugs by their various advantageous features, including sustained and controllable drug release, cellular uptake, and protection for drug therapy at extracellular and intracellular levels. − These characteristics are poised to broaden the utilization of bioactive compounds, such as plant essential oils and their derivatives, in pharmaceutical and biomedical domains. Essential oil-loaded nanodelivery systems characterized by high biodegradability and biocompatibility, such as polymer nanoparticles and liposome nanoparticles, have been researched and documented.…”