Graphical Abstract

Photochemical mechanisms of light-triggered release from nanocarriers

Nadezda Fomina, Jagadis Sankaranarayanan, Adah Almutairi

University of California San Diego, Skaggs School of Pharmacy & Pharmaceutical Sciences, Dept. of Materials Science and Engineering, Dept. of NanoEngineering, 9500 Gilman Dr. MC 0660, La Jolla, CA, USA

Received 27 July 2011, Accepted 16 February 2012, Available online 22 February 2012.

Abstract

Over the last three decades, a handful of photochemical mechanisms have been applied to a large number of nanoscale assemblies that encapsulate a payload to afford spatio-temporal and remote control over activity of the encapsulated payload. Many of these systems are designed with an eye towards biomedical applications, as spatio-temporal and remote control of bioactivity would advance research and clinical practice. This review covers five underlying photochemical mechanisms that govern the activity of the majority of photoresponsive nanocarriers: 1. photo driven isomerization and oxidation, 2. surface plasmon absorption and photothermal effects, 3. photo driven hydrophobicity changes, 4. photo driven polymer backbone fragmentation and 5. photo driven de-crosslinking. The ways in which these mechanisms have been incorporated into nanocarriers and how they affect release are detailed, as well as the advantages and disadvantages of each system.

Introduction

It is well established that nanocarriers in drug delivery offer many advantages over conventional formulation methods. They can minimize degradation of therapeutic agents upon administration, enhance their in vivo efficiency by delivering higher concentrations of drugs to tumor sites, expose the tumors to active drug for longer periods, and prevent undesirable side effects. In addition, these carriers can protect the therapeutic payload from the harsh in vivo environment. Furthermore, current studies on synergistic therapeutic outcomes of combination therapies are better enabled through the use of drug delivery vehicles.

Organic materials, both natural and synthetic, can be used to tailor nanocarriers to provide specific characteristics, including triggered release on demand. The goal of triggered drug delivery is to control the time and place of release of a therapeutic agent to achieve a higher local concentration, reduce overall injected dose, and reduce systemic toxicity.

Various internal and external triggers, such as pH, specific enzymes, temperature, ultrasound, magnetic field and light are being actively explored. Light is especially attractive, as it can be remotely applied with extremely high spatial and temporal precision. Additionally, a broad range of parameters (wavelength, light intensity, duration of exposure, and beam diameter) can be adjusted to modulate release profiles. Radiation in the UV, visible, and near infrared (NIR) regions can be applied in vivo to induce drug release. Systems responsive to UV and visible irradiation can be used for topical treatments; radiation below 650 nm cannot penetrate deeper than 1 cm into tissue due to high scattering and absorption by hemoglobin, oxy-hemoglobin, and water. NIR light of 650–900 nm (water absorbs wavelengths longer than 900 nm) can penetrate up to 10 cm [1] into living tissue and causes minimal tissue damage at the site of application.

This review focuses on light-triggered release from nanosystems. In this size regime one can passively target diseased tissues like tumors by exploiting the enhanced permeation and retention (EPR) effect while at the same time remotely and actively trigger release via light. The structure of this review reflects different mechanisms by which therapeutic agents may be released from nanocarriers upon light exposure. We cover many different nanocarrier types developed to date, including micelles, polymeric nanoparticles, hollow metal nanoparticles, and liposomes as examples of different triggering mechanisms using various photochemical reactions in order to facilitate release of cargo from the nanocarrier. All reactions lead to a change in the nanocarrier assembly either directly or indirectly, which leads to release of the encapsulated bioactive agent. While other reviews have focused on the photo-triggered release of particular nanocarriers (liposomal systems [2], [3], micelles [4], [5], [6], etc.) separately, we would like to focus on the mechanism of release rather than the nanocarrier. It should be noted that while the choice of nanocarrier can vary based on the application desired, the photochemistry involved could be applied to multiple materials and the challenges with each mechanism need to be addressed. We have also limited the scope of our review to systems for which release of cargo from nanocarriers has been demonstrated.

Section snippets

Photoisomerization, photocrosslinking, and photosensitization-induced oxidation

Photoisomerization is a process that involves a conformational change about a bond that is restricted in rotation, usually a double bond. In organic molecules with double bonds, this predominantly involves isomerization from a trans orientation to a cis form upon irradiation with light. Azobenzenes, which have NN with phenyl rings on either side, are the most commonly used molecules for this purpose. The planar trans form of azobenzenes is more hydrophobic than the nonplanar cis form, so cis

Conclusions

The use of light as an external stimulus is a promising approach to targeted drug delivery that allows precise control over the place, time, and rate of cargo release. Although the first reports of this concept appeared in the 1980s, significant progress has been made in this area over the past decade. A wide range of nanoscale assemblies have employed a handful of photochemical mechanisms to achieve efficient and reproducible release profiles. Most of the systems developed to date respond most

Acknowledgments

The authors thank the NIH Director's New Innovator Award (1 DP2 OD006499-01) and King Abdulaziz City for Science and Technology for financially supporting this work.

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