Advances in Light-Responsive Smart Multifunctional Nanofibers: Implications for Targeted Drug Delivery and Cancer Therapy

Abstract

Over the last decade, scientists have shifted their focus to the development of smart carriers for the delivery of chemotherapeutics in order to overcome the problems associated with traditional chemotherapy, such as poor aqueous solubility and bioavailability, low selectivity and targeting specificity, off-target drug side effects, and damage to surrounding healthy tissues. Nanofiber-based drug delivery systems have recently emerged as a promising drug delivery system in cancer therapy owing to their unique structural and functional properties, including tunable interconnected porosity, a high surface-to-volume ratio associated with high entrapment efficiency and drug loading capacity, and high mass transport properties, which allow for controlled and targeted drug delivery. In addition, they are biocompatible, biodegradable, and capable of surface functionalization, allowing for target-specific delivery and drug release. One of the most common fiber production methods is electrospinning, even though the relatively two-dimensional (2D) tightly packed fiber structures and low production rates have limited its performance. Forcespinning is an alternative spinning technology that generates high-throughput, continuous polymeric nanofibers with 3D structures. Unlike electrospinning, forcespinning generates fibers by centrifugal forces rather than electrostatic forces, resulting in significantly higher fiber production. The functionalization of nanocarriers on nanofibers can result in smart nanofibers with anticancer capabilities that can be activated by external stimuli, such as light. This review addresses current trends and potential applications of light-responsive and dual-stimuli-responsive electro- and forcespun smart nanofibers in cancer therapy, with a particular emphasis on functionalizing nanofiber surfaces and developing nano-in-nanofiber emerging delivery systems for dual-controlled drug release and high-precision tumor targeting. In addition, the progress and prospective diagnostic and therapeutic applications of light-responsive and dual-stimuli-responsive smart nanofibers are discussed in the context of combination cancer therapy.

General Introduction

Pharmaceutical nanotechnology has emerged as one of the most rapidly growing fields of science and technology, mainly dealing with nanoscale functional materials and nano-delivery systems (10–1000 nm) [1]. With the advancement of pharmaceutical nanotechnology, new avenues for cancer treatment have become possible through the development of various smart materials that were highly effective in overcoming the problems associated with traditional chemotherapy, which experienced deficiencies of poor aqueous solubility and bioavailability, and a lack of selectivity and specificity, resulting in unsatisfactory therapeutic outcomes and serious side effects [2]. The term “smart materials” was first coined by Toshinori Takagi in 1990 and was defined as materials whose physical properties can change in response to external stimuli [3]. At that time, the scope and feasibility of this concept were unclear, but it was expected to open up an unexplored arena in research and development. Nowadays, the term “smart materials” refers to “stimuli-responsive materials”, which have gained popularity among researchers as technology advances and novel materials are required to meet new regulatory standards. With the advancement of research, the usage of stimuli has expanded to include external stimuli such as light, electric fields, magnetic fields, and ultrasound, as well as internal stimuli such as pH, temperature, redox, and enzymes [4]. Among these smart materials are fibrous materials, which have several distinct advantages in terms of payload loading and responsive release and can be customized for specific functionalities [5]. Nanofibers are filamentous or thread-like structures, often at the nanoscale in diameter, composed of natural or synthetic polymers, or a combination of both, designed for controlled drug delivery and targeting. Their similarity to the extracellular matrix (ECM)-like structure in terms of cell adhesion, proliferation, and differentiation makes them a potential candidate for cancer therapy [6]. In addition, due to their high porosity, surface area-to-volume ratio, ease of fabrication and functionalization, and high tunability [5,6], their use as an anticancer drug delivery system has attracted much interest for potential therapeutic and diagnostic applications. However, these systems pose major challenges in terms of fiber quality and production rate, morphology and surface roughness, structural integrity and mechanical strength, surface functionalization, and stability [5,6]. Initial research on the nanofiber structure revealed a smooth surface with a solid core. However, in recent years, a variety of nanofiber topologies have emerged with potential use in drug delivery and cancer therapy. This review exhaustively portrays the latest advances in developing electro- and forcespun smart nanofibers, including light-responsive and dual-stimuli-responsive smart nanofibers. Special attention is dedicated to multifunctional, nano-in-nanofiber emerging delivery systems due to their highly tunable, dual-controlled release properties, and high-precision tumor targeting.

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Polymers commonly used in electrospinning for cancer therapy include poly-ε-caprolactone (PCL), polylactic acid (PLA), polyethylene glycol (PEG), poly(L-lactide) (PLLA), polylactic-co-glycolic acid (PLGA), polyurethane (PU), polyvinyl alcohol (PVA), polyethylene oxide (PEO), polyvinylpyrrolidone (PVP), and natural polymers like cellulose, chitosan, hyaluronic acid, collagen, and peptide.

Agiba, A.M.; Elsayyad, N.; ElShagea, H.N.; Metwalli, M.A.; Mahmoudsalehi, A.O.; Beigi-Boroujeni, S.; Lozano, O.; Aguirre-Soto, A.; Arreola-Ramirez, J.L.; Segura-Medina, P.; et al. Advances in Light-Responsive Smart Multifunctional Nanofibers: Implications for Targeted Drug Delivery and Cancer Therapy. Pharmaceutics 2024, 16, 1017. https://doi.org/10.3390/pharmaceutics16081017

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