Review Cite This: Biomacromolecules 2018, 19, 1840−1857
pubs.acs.org/Biomac
Photoresponsive Drug/Gene Delivery Systems Yang Zhou,†,§ Huan Ye,†,§ Yongbing Chen,‡ Rongying Zhu,‡ and Lichen Yin*,† †
Biomacromolecules 2018.19:1840-1857. Downloaded from pubs.acs.org by KAOHSIUNG MEDICAL UNIV on 11/09/18. For personal use only.
Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China ‡ Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China ABSTRACT: Light as an external stimulus can be precisely manipulated in terms of irradiation time, site, wavelength, and density. As such, photoresponsive drug/gene delivery systems have been increasingly pursued and utilized for the spatiotemporal control of drug/gene delivery to enhance their therapeutic efficacy and safety. In this review, we summarized the recent research progress on photoresponsive drug/gene delivery, and two major categories of delivery systems were discussed. The first category is the direct responsive systems that experience photoreactions on the vehicle or drug themselves, and different materials as well as chemical structures responsive to UV, visible, and NIR light are summarized. The second category is the indirect responsive systems that require a light-generated mediator signal, such as heat, ROS, hypoxia, and gas molecules, to cascadingly trigger the structural transformation. The future outlook and challenges are also discussed at the end.
1. INTRODUCTION
According to the different light-induced reaction pathways, the photoresponsive delivery systems can be divided into two categories: direct and indirect responsive systems (Scheme 1). Direct photoresponsive delivery means that, when absorbing light with specific wavelengths, the chemical structure of the materials can be directly transformed. Comparatively, indirect photoresponsive delivery experiences an intermediate reaction when receiving light irradiation, which generates an intermediate signal/molecule to cascadingly trigger the trans-
One of the most important challenges for drug/gene delivery is whether the drug delivery system can act at the target disease site. The development of a stimuli-responsive delivery system serves as a promising modality to meet the demand of precision delivery. With the responsiveness to a specific internal stimulus in the diseased site or an external stimulus, the delivery vehicles could allow controlled drug release to enhance the therapeutic index and reduce nonspecific toxicity.1 In other words, the right drug can be delivered to the right site at the right time. Nowadays, a variety of stimuli-responsive systems have been developed and investigated, and significant achievements have been realized. However, it also has some disadvantages due to the limitation of the stimuli. For example, pH-responsive anticancer systems may also lead to drug release in the acidic endolysosomes of normal cells to provoke side effects. Ultrasound as an external stimulus has a risk of damaging tissues or causing tumor metastasis at high intensity.2 In comparison, light as an external stimulus shows unique advantages such as spatiotemporal precision, relative safety, and minimal cross-reaction with cellular signaling networks.3−5 As a kind of electromagnetic wave, light is able to transfer a part of its energy to the exposed objects, and the transferred energy can accordingly trigger the change of the chemical bonds, chemical groups, polarity, and some other properties of the object. On this basis, photoresponsive drug/gene delivery systems have been extensively developed and explored, enabling site-specific cargo release and activation by precisely controlling the light irradiation site, dose, and duration. © 2018 American Chemical Society
Scheme 1. Various Direct and Indirect Photoresponsive Drug/Gene Delivery Systems
Special Issue: Biomacromolecules Asian Special Issue Received: March 10, 2018 Revised: April 25, 2018 Published: April 27, 2018 1840
DOI: 10.1021/acs.biomac.8b00422 Biomacromolecules 2018, 19, 1840−1857
Review
Biomacromolecules Table 1. Mechanisms of Different Light-Responsive Groups
discussed here, and they have been well-summarized in other reviews.6−9
formation of delivery vehicles or prodrugs to promote cargo release. Common mediators during indirect photoresponsive delivery include heat, reactive oxygen species (ROS), and hypoxia that can react with thermo-, ROS-, and hypoxiasensitive systems, respectively. Gas molecules can also serve as a mediator signal to either break the delivery vehicle or synergize other drugs upon light irradiation. In addition, for realizing precise control or programmed regulation of drug release, photoresponsive delivery vectors are often coupled with other stimuli-responsiveness. All these designs have highlighted the advantages of photoresponsive delivery vectors as a promising treatment paradigm. In this review, we summarize the representative studies recently reported on photoresponsive drug and gene delivery. We classify different systems based on the light source, photoresponsive element type they incorporate, and the photoresponsive pathways they undergo. In the end, the opportunities and challenges of the design of photoresponsive delivery systems are also discussed. Because this review mainly focuses on the photoresponsiveness of delivery systems in terms of structural transformation, cargo release, and cargo activation, photothermal therapy (PTT) and photodynamic therapy (PDT) that also rely on photostimulation are not
2. DIRECT PHOTORESPONSIVE DELIVERY SYSTEMS 2.1. UV-Responsive Systems. So far, the typical exposure wavelengths for photoresponsive delivery vectors are ultraviolet (UV) light (
