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Academic Journal of Medicine & Health Sciences, 2021, 2(1); doi: 10.25236/AJMHS.2021.020113.

PH-Sensitive Polymeric Nanoparticles for Targeted Delivery of Doxorubicin


Yuzhe Yuan1, Shuyao Geng2, Chenxi Li3, Jiayuan Yang4

Corresponding Author:
Yuzhe Yuan

1China Pharmaceutical University, Nanjing, Jiangsu, China

2Shandong University, Jinan, Shandong, China

3Beijing No.11 High School, Beijing, China

4Hangzhou Dianzi University, Hangzhou, Zhejiang, China

These authors contributed equally to this work


In order to improve the targeting of doxorubicin and prolong the action time of the drug, we synthesized a pH-responsive PEG-Schiff-DOX polymer prodrug loaded with nanoparticles. The nanoparticles were prepared by synthesis of PEG-CHO and condensation reaction of PEG-CHO and adriamycin. The release behavior of PEG-Schiff-DOX was tested at different pH. The morphology and particle size of these nanoparticles changed obviously after acid treatment(pH=5.0), and some of them had completely disintegrated. The narrowing of particle size distribution indicates that the heterogeneous nanoparticles disintegrate in the acidic environment of tumor cells, releasing the drug and finally achieving the maximum drug release at pH 5.0. The nanodrugs based on polymeric prodrug had advantages of simple preparation, high drug loading, good storage stability and achieve higher local drug concentration and longer drug action time under the condition of weak acid of tumor microenvironment to keep the curative effect and reduce the side effects. The advantages of offers choices for the development of new drugs and is expected to achieve good application in cancer therapy, has good prospects for development.


pH-responsive, Prodrug, Nanometer carrier, Targeted drugs

Cite This Paper

Yuzhe Yuan, Shuyao Geng, Chenxi Li, Jiayuan Yang. PH-Sensitive Polymeric Nanoparticles for Targeted Delivery of Doxorubicin. Academic Journal of Medicine & Health Sciences (2021) Vol. 2, Issue 1: 73-79. https://doi.org/10.25236/AJMHS.2021.020113.


[1] Oktay Tacar, Pornsak Sriamornsak, Crispin R Dass, Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems, Journal of Pharmacy and Pharmacology, Volume 65, Issue 2, February 2013, Pages 157–170, https://doi.org/10.1111/j.2042-7158.2012.01567.x

[2] H. Cabral, Y. Matsumoto, K. Mizuno, Q. Chen, M. Murakami, M. Kimura, Y. Terada, M.R. Kano, K. Miyazono, M. Uesaka, N.Nishiyama, K. Kataoka, Nat. Nanotechnol. 6 (2011) 815–823. 

[3] J.L. Xian, J.O. Shi, T.T. Yin, H.T. Choo, Polym. Chem. 4 (2013) 2564–2574.

[4] K.A. Abdul, Q. Dou, Z. Li, X.J. Loh, Chem. Asian. J. 11 (2016) 1300–1321.

[5] Poste G et al. Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery. Cancer Res 1982; 42: 1412–1422.

[6] Gabizon A et al.  Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies. Clin Pharmacokinet 2003; 42: 419–436.

[7] qTa  HT et al. Chitosan-diabasic orthophosphate hydrogel: a potential drug delivery system. Int J Pharmaceut 2009; 371: 134–141.

[8] Ta HT et al. A chitosan-dipotassium orthophosphate hydrogel for the delivery of doxorubicin in the treatment of osteosarcoma. Biomaterials  2009; 30: 3605–3613.

[9] Sun K et al.  Dextran-grafted–PEI nanoparticles as a carrier for co-delivery of adriamycin and plasmid into osteosarcoma cells. Int J Biol Macromol  2011; 49: 173–180.

[10] Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev (2004) 56:185–229. doi: 10.1124/ pr.56.2.6 

[11] Lyass O, Uziely B, Ben-Yosef R, Tzemach D, Heshing NI, Lotem M, et al. Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma. Cancer (2000) 89:1037– 47. doi: 10.1002/1097-0142(20000901)89:53.0.CO;2-Z

[12] Zhou N, Zhang N, Zhi Z, Jing XN, Liu DM, Shao YP, et al. One-pot synthesis of acid-degradable polyphosphazene prodrugs for efficient tumor chemotherapy. J Mater Chem B (2020) 8:10540–8. doi: 10.1039/D0TB01992E 

[13] Zhu XH, Li C, Lu Y, Liu YJ, Wan D, Zhu DW, et al. Tumor microenvironment-activated therapeutic peptide-conjugated prodrug nanoparticles for enhanced tumor penetration and local T cell activation in the tumor microenvironment. Acta Biomater (2021) 119:337–48. doi: 10.10

[14] /j.actbio.2020.11.008 16. Wen W, Guo C, Guo J. Acid-responsive adamantane-cored amphiphilic block polymers as platforms for drug delivery. Nanomaterials (2021) 11:188. doi: 10.3390/nano11010188 

[15] Cytryniak A, Nazaruk E, Bilewicz R, Górzyńska E, Ż elechowska-Matysiak K, Walczak R, et al. lipidic cubic-phase nanoparticles (cubosomes) loaded with doxorubicin and labeled with 177Lu as a potential tool for combined chemo and internal radiotherapy for cancers. Nanomaterials (2020) 10:2272. doi:10.3390/nano10112272

[16]Xin He, Dong Wang, Peng Chen, Youbei Qiao, Tiehong Yang, Zhe Yu, Chaoli Wang and Hong Wu(2020)Glioma cell-targeting doxorubicin delivery and redox-responsive release using angiopep-2 decorated carbonaceous nanodots Chem. Commun., 2020,56, 4785-4788

[17]Geldenhuys, W (Geldenhuys, Werner) Wehrung, D (Wehrung, Daniel) Groshev, A (Groshev, Anastasia) Hirani, A (Hirani, Anjali) Sutariya, V (Sutariya, Vijaykumar)(2015)PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY.,2015, 4, 497-506

[18] Chaithongyot, S (Chaithongyot, Supattra) Duangrat, R (Duangrat, Ratchanee) 1Wootthichairangsan, C (Wootthichairangsan, Chanida) Hanchaina, R (Hanchaina, Rattanavinan) Udomprasert, A (Udomprasert,Anuttara) Kangsamaksin, T (Kangsamaksin, Thaned) (2020) MATERIALS LETTERS, 260, 126952

[19] Chen, GX (Chen, Guangxiang) ,Li, D (Li, Du) ,Li, JC (Li, Jingchao) ,Luo, Y (Luo, Yu) ,Wang, JH (Wang, Jianhua), Shi, XY (Shi, Xiangyang) ,Guo, R (Guo, Rui) (2015)Targeted delivery of doxorubicin by lactobionic acid-modified laponite to hepatocarcinoma cells,JOURNAL OF CONTROLLED RELEASE 213,E34-E34

[20] Hembruff, S. L., Laberge, M. L., Villeneuve, D. J., Guo, B., Veitch, Z., Cecchetto, M., and Parissenti, A. M. (2008) Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance BMC Cancer 8, 318

[21] Horton, K. L., Stewart, K. M., Fonseca, S. B., Guo, Q., and Kelley, S. O. (2008) Mitochondria-penetrating peptides Chem. Biol. 15, 375– 382[Crossref], [PubMed], [CAS], Google Scholar

[22] Yousif, L. F., Stewart, K. M., Horton, K. L., and Kelley, S. O. (2009) Mitochondria-penetrating peptides:sequence effects and model cargo transport ChemBioChem 10, 2081– 2088[Crossref], [PubMed], [CAS], [Google Scholar]

[23] R.B. Greenwald, J. Controlled, Release 74 (2001) 159–171.

[24] J.M. Harris, R.B. Chess, Nat. Rev. Drug Discov. 2 (2003) 214–221.

[25] T. Luo, C. Loira-Pastoriza, H.P. Patil, B. Ucakar, G.G. Muccioli, C. Bosquillon, R. Vanbever, J. Control. Release 239 (2016) 62–71.

[26] X. Wang, D. Li, F. Yang, H. Shen, Z. Li, D. Wu, Polym. Chem. 4 (2013) 4596–4600.

[27] S.S. Liow, Q. Dou, D. Kai, Z. Li, S. Sugiarto, C.Y.Y. Yu, R.T.K. Kwok, X. Chen,Y.L. Wu, S.T. Ong, A. Kizhakeyil, N.K. Verma, B.Z. Tang, X.J. Loh, Small 13 (2017) 1603404.

[28] D. Li, Y. Bu, L. Zhang, X. Wang, Y. Yang, Y. Zhuang, F. Yang, H. Shen, D. Wu,Biomacromolecules 17 (2016) 291–300.

[29] H. Gelderblom, J. Verweij, K. Nooter, A. Sparreboom, Eur. J. Cancer 37 (2001)1590–1598.

[30] C. Zheng, H. Gao, D.P. Yang, M. Liu, H. Cheng, Y.L. Wu, J.L. Xian, Mater. Sci. Eng. C74 (2017) 110–116.