Smart Nanosystems for Overcoming Multiple Biological Barriers in Cancer Nanomedicines Transport: Design Principles, Progress, and Challenges

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2023-07, Vol.19 (28), p.e2207973-n/a
• Main Authors: Lin, Gan, Zhou, Jiajing, Cheng, Hongwei, Liu, Gang
• Format: Article
• Language: English
• Subjects: Accumulation; biological barriers; Blood circulation; cancer therapy; Controlled release; Drug Carriers - chemistry; drug delivery; Drug Delivery Systems; Endosomes; Humans; Nanomedicine; Nanotechnology; Neoplasms - drug therapy; Neoplasms - pathology; Principles; Proteins - therapeutic use; smart nanosystems; Tumor Microenvironment; Tumors
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202207973

The development of smart nanosystems, which could overcome diverse biological barriers of nanomedicine transport, has received intense scientific interest in improving the therapeutic efficacies of traditional nanomedicines. However, the reported nanosystems generally hold disparate structures and functions, and the knowledge of involved biological barriers is usually scattered. There is an imperative need for a summary of biological barriers and how these smart nanosystems conquer biological barriers, to guide the rational design of the new‐generation nanomedicines. This review starts from the discussion of major biological barriers existing in nanomedicine transport, including blood circulation, tumoral accumulation and penetration, cellular uptake, drug release, and response. Design principles and recent progress of smart nanosystems in overcoming the biological barriers are overviewed. The designated physicochemical properties of nanosystems can dictate their functions in biological environments, such as protein absorption inhibition, tumor accumulation, penetration, cellular internalization, endosomal escape, and controlled release, as well as modulation of tumor cells and their resident tumor microenvironment. The challenges facing smart nanosystems on the road heading to clinical approval are discussed, followed by the proposals that could further advance the nanomedicine field. It is expected that this review will provide guidelines for the rational design of the new‐generation nanomedicines for clinical use. Smart nanosystems with multiple functions, including specific surface, transformable ability, tumor microenvironment modulating and tumor cells regulating and etc., are overviewed to overcome the biological barriers in cancer therapy, followed by the brief discussion of several considerations on translational barriers to advance the developed nanosystems towards clinical use.