Construction and <i>in vitro</i> evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)<sub>10</sub>-MAP nanoparticles

YONG Qin; YUE Hanxun; SHI Min; HUANG Shiqin; ZHAO Xuan; YU Xian

doi:10.11665/j.issn.1000-5048.20210306

Journal of China Pharmaceutical University > 2021 > 52(3): 301-310. > DOI: 10.11665/j.issn.1000-5048.20210306

YONG Qin, YUE Hanxun, SHI Min, HUANG Shiqin, ZHAO Xuan, YU Xian. Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)₁₀-MAP nanoparticles[J]. Journal of China Pharmaceutical University, 2021, 52(3): 301-310. DOI: 10.11665/j.issn.1000-5048.20210306

Citation:

PDF (4610 KB)

Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)₁₀-MAP nanoparticles

1.
Phase I Clinical Trial Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010
2.
Department of Pharmacy, Central Hospital of Luohe, Luohe 462000
3.
Department of Pharmacy, Central Hospital of Jiangjin District, Chongqing 402260, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 82072327)

More Information

Received Date: November 29, 2020
Revised Date: May 25, 2021

Graphical Abstract

Abstract

Abstract

To construct PTEN/PLGA-(HE)₁₀-MAP nanoparticles, which encapsulated PTEN plasmid DNA and combined with the pH-responsive cell-penetrating peptides (CPPs), and to investigate their effects of gene delivery and anti-tumor targets in vitro. Poly (lactic-co-glycolic acid) (PLGA) nanoparticles loaded with PTEN plasmid DNA were prepared by double emulsification-solvent evaporation method. PTEN/PLGA-(HE)₁₀-MAP nanoparticles were prepared by coupling the histidine-glutamic acid-model amphipathic peptide nanocomplex [(HE)₁₀-MAP] to the surface through amide condensation reaction. Particle size, Zeta potential, encapsulation rate and drug loading were tested to characterize the nanoparticles. By analyzing the cytotoxicity, cellular uptake, targeted transfection of eukaryotic expression plasmids and anti-tumor cell proliferation, the feasibility as a targeted gene delivery system were evaluated. The particle size of PTEN/PLGA-(HE)₁₀-MAP nanoparticles was (266.5 ± 2.86) nm, with the encapsulation efficiency (80.6 ± 6.11)%. Zeta potentials were -(6.7 ± 0.26) mV, +(0.7 ± 0.22) mV and +(37.5 ± 0.85) mV at pH 7.4, 7.0 and 6.5, respectively. In the cytotoxicity test, the cell survival rates of tumor and normal cells were above 80%.Non-loading PLGA-(HE)₁₀-MAP nanoparticles showed no obvious cytotoxicity. The results of cellular uptake experiments showed that PTEN/PLGA-(HE)₁₀-MAP nanoparticles were more readily taken up by cells.The results of CCK-8 showed that the nanoparticles could pH-specifically inhibit proliferation of tumor cell in vitro.And PTEN/PLGA-(HE)₁₀-MAP nanoparticles may be applied in tumor gene therapy.
- nanoparticle,
- pH-responsive,
- PLGA,
- tumor-targeted,
- cell-penetrating peptides,
- gene delivery

FullText(HTML)

References (26)

References

[1]	. CA Cancer J Clin，2021，71（3）：209-249.
[2]	Bromma K，Chithrani DB. Advances in gold nanoparticle-based combined cancer therapy［J］. Nanomaterials （Basel），2020，10（9）：E1671.
[3]	Oliver R. Principles and practice of the biologic therapy of cancer （third edition）［J］. Br J Cancer，2002，86（4）：662-663.
[4]	Li J，Yen C，Liaw D，et al. PTEN，a putative protein tyrosine phosphatase gene mutated in human brain，breast，and prostate cancer［J］. Science，1997，275（5308）：1943-1947.
[5]	Yu X，Li TT，Xia YF，et al. Herpes simplex virus type 1 VP22-mediated intercellular delivery of PTEN increases the antitumor activity of PTEN in esophageal squamous cell carcinoma cells in vitro and in vivo［J］. Oncol Rep，2016，35（5）：3034-3040.
[6]	Sun ZG，Ji N，Bi MM，et al. Negative expression of PTEN identifies high risk for lymphatic-related metastasis in human esophageal squamous cell carcinoma［J］. Oncol Rep，2015，33（6）：3024-3032.
[7]	Li X，Guo S，Min L，et al. miR-92a-3p promotes the proliferation，migration and invasion of esophageal squamous cell cancer by regulating PTEN［J］. Int J Mol Med，2019，44（3）：973-981.
[8]	Kormann MS，Hasenpusch G，Aneja MK，et al. Expression of therapeutic proteins after delivery of chemically modified mRNA in mice［J］. Nat Biotechnol，2011，29（2）：154-157.
[9]	Liu HY，Li LF，Xu CX，et al. Preparation of pitavastatin-loaded poly lactic-co-glycolic acid nanoparticles and their effects on proliferation of endothelial progenitor cells［J］. J China Pharm Univ（中国药科大学学报），2016，47（2）：166-170.
[10]	Ratzinger G，Agrawal P，K?rner W，et al. Surface modification of PLGA nanospheres with Gd-DTPA and Gd-DOTA for high-relaxivity MRI contrast agents［J］. Biomaterials，2010，31（33）：8716-8723.
[11]	Steiner V，Sch?r M，B?rnsen KO，et al. Retention behaviour of a template-assembled synthetic protein and its amphiphilic building blocks on reversed-phase columns［J］. J Chromatogr，1991，586（1）：43-50.
[12]	Zaro JL，Fei LK，Shen WC. Recombinant peptide constructs for targeted cell penetrating peptide-mediated delivery［J］. J Control Release，2012，158（3）：357-361.
[13]	Yu X，Xu Z，Lei J，et al. VP22 mediates intercellular trafficking and enhances the in vitro antitumor activity of PTEN［J］. Mol Med Rep，2015，12（1）：1286-1290.
[14]	Huang SQ，Shi M，He YN，et al. Construction and in vitro evaluation of DC-targeted aptamer-modified Pseudomonas aeruginosa DNA vaccine delivery system［J］. J China Pharm Univ（中国药科大学学报），2019，50（6）：743-752.
[15]	Jensen DK，Jensen LB，Koocheki S，et al. Design of an inhalable dry powder formulation of DOTAP-modified PLGA nanoparticles loaded with siRNA［J］. J Control Release，2012，157（1）：141-148.
[16]	Yang N，Jiang Y，Zhang HF，et al. Active targeting docetaxel-PLA nanoparticles eradicate circulating lung cancer stem-like cells and inhibit liver metastasis［J］. Mol Pharm，2015，12（1）：232-239.
[17]	Shen M，Huang Y，Han L，et al. Multifunctional drug delivery system for targeting tumor and its acidic microenvironment［J］. J Control Release，2012，161（3）：884-892.
[18]	Tahara K，Sakai T，Yamamoto H，et al. Establishing chitosan coated PLGA nanosphere platform loaded with wide variety of nucleic acid by complexation with cationic compound for gene delivery［J］. Int J Pharm，2008，354（1/2）：210-216.
[19]	Peres C，Matos AI，Conniot J，et al. Poly（lactic acid）-based particulate systems are promising tools for immune modulation［J］. Acta Biomater，2017，48：41-57.
[20]	Felber AE，Dufresne MH，Leroux JC. pH-sensitive vesicles，polymeric micelles，and nanospheres prepared with polycarboxylates［J］. Adv Drug Deliv Rev，2012，64（11）：979-992.
[21]	Sarko D，Beijer B，Garcia Boy R，et al. The pharmacokinetics of cell-penetrating peptides［J］. Mol Pharm，2010，7（6）：2224-2231.
[22]	Fei L，Yap LP，Conti PS，et al. Tumor targeting of a cell penetrating peptide by fusing with a pH-sensitive histidine-glutamate co-oligopeptide［J］. Biomaterials，2014，35（13）：4082-4087.
[23]	Kenien R，Zaro JL，Shen WC. MAP-mediated nuclear delivery of a cargo protein［J］. J Drug Target，2012，20（4）：329-337.
[24]	Patel VR，Agrawal YK. Nanosuspension：an approach to enhance solubility of drugs［J］. J Adv Pharm Technol Res，2011，2（2）：81-87.
[25]	Adegoke O，Park EY. Gold nanoparticle-quantum dot fluorescent nanohybrid：application for localized surface plasmon resonance-induced molecular beacon ultrasensitive DNA detection［J］. Nanoscale Res Lett，2016，11（1）：523.
[26]	Vercauteren D，Rejman J，Martens TF，et al. On the cellular processing of non-viral nanomedicines for nucleic acid delivery：mechanisms and methods［J］. J Control Release，2012，161（2）：566-581.

Cited By

Get Citation

PDF

XML

Article views (164) PDF downloads (725)

Turn off MathJax

Article Contents

Abstract

References

Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)10-MAP nanoparticles

Abstract

References

Catalog

Export File

Citation

Format

Content

Construction and in vitro evaluation of pH-responsive and tumor-targeted PTEN/PLGA-(HE)₁₀-MAP nanoparticles