Charge-reversal Nanoparticles: Novel Targeted Drug Delivery Carriers

Authors: Xinli Chena, Lisha Liua, Chen Jianga


Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).

Key words

Cancer therapy; Charge-reversal nanoparticles; Drug delivery carriers; Stimuli responsive; Nanotechnology.

Citation: Xinli Chena, Lisha Liua, Chen Jianga Charge-reversal Nanoparticles: Novel Targeted Drug Delivery Carriers doi:10.1016/j.apsb.2016.05.011.

Received: 28 April 2016, Revised: 15 May 2016, Accepted: 16 May 2016, Available online: 8 June 2016

Copyright: © 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (


The design of a drug delivery system often uses a specific ligand for a tumor target. However, less than 5% of the dosage of an intravenous injection is able to reach the tumor site. Smart nanocarriers sensitive to exogenous or endogenous stimuli represent an alternative targeted drug delivery method. A wide range of stimuli is able to trigger drug release at the desired place and time, and the diversity of responsive materials has been assembled in different architectures, allowing great flexibility in the design of stimuli-responsive systems on-demand.

Charge-reversal delivery strategies are designed to be sensitive to specific stimuli, such as a lowered interstitial pH, a higher glutathione concentration, or an increased level of certain enzymes such as MMP. At the cellular level, pH sensitivity can either trigger the release of the transported drug into late endosomes or lysosomes, or promote the escape of the nanocarriers from the lysosomes to the cell cytoplasm. At the tissue level, one can take advantage of specific microenvironmental changes associated with neoplastic diseases (the treatment of which is the focus of most research efforts on stimuli-responsive nanocarriers) as well as pathological situations, such as ischemia, inflammatory diseases or infections. The ability to switch the surface charge allows one to avoid the unspecific absorption and enhance the tumor target delivery.

As discussed in this review, considerable progress in materials chemistry and drug delivery has led to the design of charge-reversal concepts using well-engineered nanosystems. The focus should now shift towards clinically acceptable systems that are more sensitive to discrete variations in specific stimuli. We believe that charge-reversal drug delivery strategies for targeting tumor treatment will provide promising avenues to treat cancers in the future.