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Stimuli-Responsive Polymeric Nanocarriers for Efficient Gene Delivery

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Abstract

Gene therapy provides an alternative and effective method for treatment of genetic diseases and cancers that are refractory to conventional therapeutics. The success of gene therapy is largely dependent on the development of safe and effective gene delivery vectors for transporting genetic material from the blood stream to the cytoplasm or nucleus. Current gene vectors can be divided into viral and non-viral vectors. Although non-viral gene delivery carriers can offer some advantages, such as safety and facile fabrication, they do not possess the same high gene transfection efficiency as viral vectors due to a lack of functionality to overcome extra- and intracellular gene delivery obstacles. On the basis of these disadvantages, researchers are developing “smart” non-viral gene-delivery carriers in order to overcome the physiological barriers and realize efficient gene transfection. These “smart” stimuli-responsive carriers can undergo physical or chemical reactions in response to internal tumor-specific environments, such as pH conditions, redox potentials, enzymatic activations and thermal gradients, as well as external stimulations, such as ultrasound, light, magnetic fields, and electrical fields. Furthermore, “smart” carriers can also be triggered by dual or multiple combinations of different stimuli. In this review, we highlight the recent stimuli-sensitive polymeric nanocarriers for gene delivery, and we discuss the potential of combining multiple stimuli-responsive strategies for future gene therapy applications.

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Abbreviations

AAm:

Acrylamide

AAV:

Adeno-associated viruses

ADV:

Acoustic droplet vaporization

AON:

Antisense oligodeoxy nucleotides

ATP:

Adenosine triphosphate

azoTAB:

Azobenzene-trimethylammonium bromide

BAH:

Bis-aryl hydrazone

C11F17-PAsp(DET):

C11F17-poly[N-[N′-(2-aminoethyl)]aspartamide]

CMD:

Carboxymethyl dextran

CPDT:

Cyclopentadithiophene

CTX:

Chlorotoxin

DSPEI:

Degradability of disulfide cross-linked short PEIs

dtACPP:

Activatable cell-penetrating peptide

GALA:

Glutamic acid-alanine-leucine-alanine

GFP:

Green fluorescent protein

GILT:

Gamma-interferon-inducible lysosomal thiol reductase

GNR:

Gold nanorod

GSH:

Gutathione

HCC:

Hepatocellular carcinoma

HHV:

Herpes simplex viruses

KALA:

Lysine-alanine-leucine-alanine

KAPE:

Ketal containing poly (β-amino esters)

LCST:

Low critical solution temperature

MB:

Microbubble

MF:

Magnetic field

MMA:

Methyl methacrylate

MMPs:

Matrix metalloproteinases

MN core:

Magnetic nanopartical core

MPAP:

Membrane translocation peptides

mPEG-b-PLLys:

Poly(ethylene glycol)-b-poly(l-lysine)

NBU:

o-Nitrobenzyl urethane

NIR:

Near infrared

NS:

Nanoshell

PAA:

Poly (acrylic acid)

PAO:

Poly(alkylene oxides)

PATK:

Poly(amino thioketal)

PBA:

Phenylboronic acid

PBAA:

Poly (butyl acrylicacid)

PBAE:

Poly(β-amino ester)

PDEA:

Poly(2-(diethylamino)ethyl methacrylate)

PDMAEMA:

Poly(2-dimethylaminoethyl methacrylate)

PEAA:

Poly(ethyl acrylic acid)

PEEP-b-PDMAEMA:

Poly(ethylethylene phosphate)-block-poly[2-(dimethylamino)ethyl methacrylate]

PEG:

Polyethylene glycol

PEI:

Polyethylenimine

PEO-PPO-PEO:

Poly-(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)

PFP:

Perfluoropentane

PGA-g-mPEG:

Poly(glutamic acid)-g-MeO-poly(ethylene glycol)

PICM:

PEG-b-P (PrMA-co-MAA)

PLH:

Poly (l-histidine)

PLL:

Poly-l-lysine

PLys:

Poly (l-lysine)

PMA:

Poly (meth acrylic acid)

PNIPAM:

Poly (N-isopropylacrylamide)

PPAA:

Poly (propyl acrylic acid)

PPDDP:

MPEG113-b-CP5k-b-PDMAEMA42-b-P(DMAEMA22-co-BMA40-co-PAA24

PPMCs:

Pluronic/polyethylenimine to embedded magnetite nanocrystals

PPPs:

Photo- and pH-responsive polypeptides

PTX:

Paclitaxel

RES:

Reticuloe endothelin system

ROS:

Reactive oxygen species

SDBS:

Sodium dodecylbenzenesulfonate

SDS:

Sodium dodecylsulfate

siGFP:

siRNA molecules targeting GFP

SPIO:

Superparamagnetic oxide nanoparticle

SSPEI:

Disulfide-containing polyethylenimine

UCAs:

Ultrasound contrast agents

UCST:

Upper critical solution temperature

UNCs:

Upconversion nanoparticles

uPA:

Urokinase plasminogen activator

US:

Ultrasound contrast agents

VP:

Vinylpyrrolidinone

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (51225305, U1401242), the Natural Science Foundation of Guangdong Province (2016A030313315, 2014A030312018), the Science and Technology Planning Project of Guangdong Province (2015A050502024), the Tip-top Scientific and Technical Innovative Youth Talents of Guangdong Special Support Program (2014TQ01R651), the Fundamental Research Funds for the Central Universities (161gzd05) and the China Scholarship Council (CSC).

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    1. Department of Biomedical Engineering, School of Engineering, Sun Yat-sen University, Guangzhou, 510006, Guangdong, China

      Yingqin Li, Jinbiao Gao, Chao Zhang, Zhong Cao & Jie Liu

    2. PCFM Lab of Ministry of Education, School of Material Science and Engineering, Sun Yat-sen University, Guangzhou, 510275, China

      Du Cheng & Xintao Shuai

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    1. Yingqin Li
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    Correspondence to Jie Liu or Xintao Shuai.

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    Y. Li and J. Gao contributed equally to this work.

    This article is part of the Topical Collection “Polymeric Gene Delivery Systems”; edited by Yiyun Cheng.

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    Li, Y., Gao, J., Zhang, C. et al. Stimuli-Responsive Polymeric Nanocarriers for Efficient Gene Delivery. Top Curr Chem (Z) 375, 27 (2017). https://doi.org/10.1007/s41061-017-0119-6

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