Subscriber access provided by Monroe Library | Loyola University New Orleans
Review
Photo-Responsive Drug/Gene Delivery Systems Yang Zhou, Huan Ye, Yongbing Chen, Rongying Zhu, and Lichen Yin Biomacromolecules, Just Accepted Manuscript • DOI: 10.1021/acs.biomac.8b00422 • Publication Date (Web): 27 Apr 2018 Downloaded from http://pubs.acs.org on April 27, 2018
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 66 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
Photo-Responsive Drug/Gene Delivery Systems Yang Zhou1,‡, Huan Ye1,‡, Yongbing Chen2, Rongying Zhu2, Lichen Yin1,* 1
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. 2
Department of Cardiothoracic Surgery, the Second Affiliated Hospital of Soochow University,
Suzhou 215004, China.
‡These authors contributed equally to this work. *
Correspondence should be addressed to L.Y. (
[email protected]).
KEYWORDS: photo-responsiveness, drug/gene delivery, photoreaction, structural conformation, controlled release
ABSTRACT
Light as an external stimulus can be precisely manipulated in terms of irradiation time, site, wavelength, and density. As such, photo-responsive 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
ACS Paragon Plus Environment
1
Biomacromolecules 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 2 of 66
progresses on photo-responsive 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 in the end.
TEXT 1. Introduction One of the most important challenges for drug/gene delivery is whether the drug delivery system can act at the target disease site. Development of 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 non-specific toxicity.1 In other words, the right drug can be delivered to the right site at the right time. Nowadays, varieties of stimuli-responsive systems have been developed and investigated, and great achievements have been realized. However, it also has some disadvantages due to the limitation of the stimuli. For example, pH-responsive anti-cancer systems may also lead to drug release in the acidic endolysosomes of normal cells to provoke side effect. 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
ACS Paragon Plus Environment
2
Page 3 of 66 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Biomacromolecules
precision, relative safety, and minimal cross-reaction with cellular signaling networks.3-5 As a kind of electromagnetic waves, 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. Based on this, photo-responsive 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. According to the different light-induced reaction pathways, the photo-responsive delivery systems can be divided into two categories, direct responsive and indirect responsive systems. Direct photo-responsive 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 transformation 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 hypoxia-sensitive 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, in order to realize precise control or programmed regulation of drug release, photo-responsive delivery vectors are often coupled with other stimuli-responsiveness. All these designs have highlighted the advantages of photo-responsive delivery vectors as a promising treatment paradigm. In this review, we summarize the representative studies recently reported on photo-responsive drug and gene delivery. We classify different systems based on the light source, photoresponsive element type they incorporate, and the photo-responsive pathways they undergo. In
ACS Paragon Plus Environment
3
Biomacromolecules 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Page 4 of 66
the end, the opportunities and challenges of the design of photo-responsive delivery systems are also discussed. Since this review mainly focuses on the photo-responsiveness of delivery systems in terms of structural transformation, cargo release, and cargo activation, photothermal therapy (PTT) and photodynamic therapy (PDT) that also rely on photo-stimulation are not discussed here, and they have been well summarized in other reviews.6-9
Scheme 1. Various direct and indirect photo-responsive drug/gene delivery systems.
2. Direct photo-responsive delivery systems 2.1. UV-responsive systems So far, the typical exposure wavelengths for photo-responsive delivery vectors are ultraviolet (UV) light (
