Recent advances in co-delivery systems based on polymeric nanoparticle for cancer treatment

Figures & data

Table 1. Some examples of polymeric nanoparticles employed as co-delivery systems.

Nanoparticle	Polymer	Drug-drug or Drug-gene	Assay condition	Reference
Polymeric micelles	P(MDS-co-CES)	Paclitaxel and Herceptin	in vitro	[14]
	EG-acid diblock copolymer PEG-PAC (or PEG-P(MTC-OH))	Thioridazine and doxorubicin	in vitro and in vivo	[15]
	A ternary block copolymer PEG- PAsp(AED)-PDPA	Doxorubicin and BCL2 siRNA	in vivo	[8]
	Pluronic(®) micelles	Resveratrol and curcumin	in vitro	[16]
	PDMAEMA-PCL-PDMAEMA triblock copolymers	Paclitaxel and VEGF SiRNA	in vitro	[17]
	PDP-PDHA	Doxorubicin and Survivin-targeting shRNA	in vitro and in vivo	[18]
	POSS-based star-shaped	Doxorubicin and P53 plasmid DNA	in vitro and in vivo	[19]
	PEG-pp-PEI-PE	Paclitaxel and free-SiRNA	in vitro and in vivo	[20]
	A ternary block copolymer PEG-PAsp(AED)-PDPA	Doxorubicin and BCL2 SiRNA	in vitro and in vivo	[21]
Dendrimers	MPEG-b-PAMAM	10-hydroxy-camptothecin and doxorubicin	in vitro and in vivo	[22]
	A three-layered telodendrimer micelles (TM)	Cisplatin and paclitaxel	in vitro and in vivo	[23]
	PAMAM-PEG-T7	Doxorubicin and plasmid pORF-hTRAIL	in vitro and in vivo	[24]
	G(4)-PAMAM	Docetaxel and SiRNA	in vitro	[25]
	PAMAM	5-Fluorouracil and miR-21	in vitro	[26]
	PAMAM-HA	Doxorubicin and MVP-siRNA	in vivo	[27]
	CD-PLLD	Docetaxel and MMP-9 siRNA	in vitro and in vivo	[28]
Poly(dl-lactide co-glycolide) (PLGA)	PLGA	Docetaxel and vitamin E TPGS	in vitro and in vivo	[29]
	PEG-PLGA copolymer	Doxorubicin and paclitaxel	in vitro	[30]
	PLGA-TPGS	Docetaxel and poloxamers 235	in vitro and in vivo	[31]
	PLGA	Rapamycin and piperine	in vitro and in vivo	[32]
	mPEG-PLGA	SH-aspirin and curcumin	in vitro	[33]
	MLNP	Camptothecin and pTRAIL	in vitro and in vivo	[34]
	PCNPs	Doxorubicin and free-SiRNA	in vitro and in vivo	[35]
	PLGA	Paclitaxel and Stat3 SiRNA	in vitro	[36]
	PLGA-b-PEG	Antisense-miR-10b and antisense-miR-21	in vitro and in vivo	[37]
	PLGA/PF127	Doxorubicin and miR-542-3P	in vitro	[38]
	PLGA/PEI	Doxorubicin and anti Bcl-xL shRNA	in vitro	[39]
	PLGA/PEG	Metformin and curcumin	in vitro	[40]
Chitosan (CS)	CS	Camptothecin and curcumin	in vitro	[41]
	PEGylated CS	Methotrexate and mitomycin	in vitro and in vivo	[42]
	Pluronic F127-chitosan	Doxorubicin and paclitaxel	in vitro and in vivo	[43]
	CPC	Candesartan and Wt-p53	in vitro and in vivo	[44]
	CLP	Paclitaxel and free-SiRNA	in vitro	[45]
	CS	Doxorubicin and mi-34a	in vitro and in vivo	[46]
	CS	Gefitinib and shMDR1	in vitro	[47]
	CS	Doxorubicin and IGF-1R siRNA	in vitro	[48]
poly(ethylenimine) (PEI)	mPEG-PCL-g-PEI	Doxorubicin and plasmid DNA	in vitro and in vivo	[49]
	PELG/PEI	Cis-aconityl-doxorubicin and P53 plasmid DNA	in vitro and in vivo	[50]
	PEI-SA	Doxorubicin and VEGF SiRNA	in vivo	[51]
	LMw-PEI/PCL	Doxorubicin and P53 plasmid DNA	in vitro	[52]
Poly(l-lysine) (PLL)	mPEsG-b-PLG-b-PLL/DOCA	Doxorubicin and paclitaxel	in vitro and in vivo	[53]
	G3-[PEG-RGD]	Doxorubicin and SiRNA	in vivo	[54]
	PEG-PLL-PL-Leu	Docetaxel and SiRNA-BCL2	in vitro and in vivo	[55]
	CD-PLLD	Docetaxel and MMP-9 SiRNA plasmid	in vitro and in vivo	[28]
	PP-PLLD-Arg	Docetaxel and MMP-9 shRNA	in vitro and in vivo	[56]

Figure 1. Schematic representation of polymeric micelles. Adapted from the published works of Xu et al. [57].

Figure 2. Co-delivery of thioridazine and doxorubicin using polymeric micelles. Adapted from the published works of Ke et al. [15].

Figure 3. Co-delivery of siRNA and paclitaxel by biodegradable cationic micelles composed of PDMAEMA–PCL–PDMAEMA copolymers Adapted from the published works of Zhu et al. [17].

Figure 4. Schematic presentation of dendrimers. Adapted from the published works of Debnath et al. [128].

Figure 5. Hydrolysis of poly-d,l-lactide-co-glycolide nanoparticles. Adapted from the published works of Kumari et al. [82].

Figure 6. Chemical structure of chitosan. Adapted from the published works of Younes et al. [129].

Figure 7. Development of both methotrexate and mitomycin C loaded PEGylated chitosan nanoparticles for targeted drug co-delivery and synergistic anticancer effect. Adapted from the published works of Jia et al. [42].

Figure 8. A chitosan-graft-PEI-candesartan conjugate for targeted co-delivery of drug and gene in anti-angiogenesis cancer therapy. Adapted from the published works of Bao et al. [44].

Figure 9. Chemical structure of polyethyleneimine. Adapted from the published works of Liu et al. [130].

Figure 10. Co-delivery of antitumor drug and gene by a pH-sensitive charge-conversion system. Adapted from the published works of et al. [50].

Lee AL, Wang Y, Cheng HY, et al. The co-delivery of paclitaxel and Herceptin using cationic micellar nanoparticles. Biomaterials. 2009;30:919–927.

 PubMed Web of Science ®Google Scholar

Ke XY, Ng VWL, Gao SJ, et al. Co-delivery of thioridazine and doxorubicin using polymeric micelles for targeting both cancer cells and cancer stem cells. Biomaterials. 2014;35:1096–1108.

 PubMed Web of Science ®Google Scholar

Kang L, Gao Z, Huang W, et al. Nanocarrier-mediated co-delivery of chemotherapeutic drugs and gene agents for cancer treatment. Acta Pharmaceutica Sinica B. 2015;5:169–175.

 PubMed Web of Science ®Google Scholar

Carlson LJ, Cote B, Alani AW, et al. Polymeric micellar co‐delivery of resveratrol and curcumin to mitigate in vitro doxorubicin‐induced cardiotoxicity. J Pharm Sci. 2014;103:2315–2322.

 PubMed Web of Science ®Google Scholar

Zhu C, Jung S, Luo S, et al. Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA–PCL–PDMAEMA triblock copolymers. Biomaterials. 2010;31:2408–2416.

 PubMed Web of Science ®Google Scholar

Tang S, Yin Q, Zhang Z, et al. Co-delivery of doxorubicin and RNA using pH-sensitive poly (β-amino ester) nanoparticles for reversal of multidrug resistance of breast cancer. Biomaterials. 2014;35:6047–6059.

 PubMed Web of Science ®Google Scholar

Li Y, Xu B, Bai T, et al. Co-delivery of doxorubicin and tumor-suppressing p53 gene using a POSS-based star-shaped polymer for cancer therapy. Biomaterials. 2015;55:12–23.

 PubMed Web of Science ®Google Scholar

Zhu L, Perche F, Wang T, et al. Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific co-delivery of siRNA and hydrophobic drugs. Biomaterials. 2014;35:4213–4222.

 PubMed Web of Science ®Google Scholar

Chen W, Yuan Y, Cheng D, et al. Co‐delivery of doxorubicin and siRNA with reduction and pH dually sensitive nanocarrier for synergistic cancer therapy. Small. 2014;10:2678–2687.

 PubMed Web of Science ®Google Scholar

Zhang Y, Xiao C, Li M, et al. Co‐delivery of 10‐hydroxycamptothecin with doxorubicin conjugated prodrugs for enhanced anticancer efficacy. Macromol Biosci. 2013;13:584–594.

 PubMed Web of Science ®Google Scholar

Cai L, Xu G, Shi C, et al. Telodendrimer nanocarrier for co-delivery of paclitaxel and cisplatin: a synergistic combination nanotherapy for ovarian cancer treatment. Biomaterials. 2015;37:456–468.

 PubMed Web of Science ®Google Scholar

Han L, Huang R, Li J, et al. Plasmid pORF-hTRAIL and doxorubicin co-delivery targeting to tumor using peptide-conjugated polyamidoamine dendrimer. Biomaterials. 2011;32:1242–1252.

 PubMed Web of Science ®Google Scholar

Biswas S, Deshpande PP, Navarro G, et al. Lipid modified triblock PAMAM-based nanocarriers for siRNA drug co-delivery. Biomaterials. 2013;34:1289–1301.

 PubMed Web of Science ®Google Scholar

Ren Y, Kang CS, Yuan XB, et al. Co-delivery of as-miR-21 and 5-FU by poly (amidoamine) dendrimer attenuates human glioma cell growth in vitro. J Biomater Sci Polym Ed. 2010;21:303–314.

 PubMed Web of Science ®Google Scholar

Han M, Lv Q, Tang XJ, et al. Overcoming drug resistance of MCF-7/ADR cells by altering intracellular distribution of doxorubicin via MVP knockdown with a novel siRNA polyamidoamine-hyaluronic acid complex. J Control Release. 2012;163:136–144.

 PubMed Web of Science ®Google Scholar

Liu T, Xue W, Ke B, et al. Star-shaped cyclodextrin-poly(l-lysine) derivative co-delivering docetaxel and MMP-9 siRNA plasmid in cancer therapy. Biomaterials. 2014;35:3865–3872.

 PubMed Web of Science ®Google Scholar

Zhu H, Chen H, Zeng X, et al. Co-delivery of chemotherapeutic drugs with vitamin E TPGS by porous PLGA nanoparticles for enhanced chemotherapy against multi-drug resistance. Biomaterials. 2014;35:2391–2400.

 PubMed Web of Science ®Google Scholar

Wang H, Zhao Y, Wu Y, et al. Enhanced anti-tumor efficacy by co-delivery of doxorubicin and paclitaxel with amphiphilic methoxy PEG-PLGA copolymer nanoparticles. Biomaterials. 2011;32:8281–8290.

 PubMed Web of Science ®Google Scholar

Tang X, Liang Y, Feng X, et al. Co-delivery of docetaxel and poloxamer 235 by PLGA–TPGS nanoparticles for breast cancer treatment. Mater Sci Eng C Mater Biol Appl. 2015;49:348–355.

 PubMed Web of Science ®Google Scholar

Katiyar S, Muntimadugu SE, Rafeeqi TA, et al. Co-delivery of rapamycin-and piperine-loaded polymeric nanoparticles for breast cancer treatment. Drug Deliv. 2016;23:2608–2616.

 PubMed Web of Science ®Google Scholar

Zhou L, Duan X, Zeng S, et al. Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis. Int J Nanomedicine. 2015;10:5205.

 PubMed Web of Science ®Google Scholar

Ediriwickrema A, Zhou J, Deng Y, et al. Multi-layered nanoparticles for combination gene and drug delivery to tumors. Biomaterials. 2014;35:9343–9354.

 PubMed Web of Science ®Google Scholar

Liu H, Li Y, Mozhi A, et al. SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment. Biomaterials. 2014;35:6519–6533.

 PubMed Web of Science ®Google Scholar

Su WP, Cheng FY, Shieh DB, et al. PLGA nanoparticles codeliver paclitaxel and Stat3 siRNA to overcome cellular resistance in lung cancer cells. Int J Nanomedicine. 2012;7:4269–4283.

 PubMed Web of Science ®Google Scholar

Devulapally R, Sekar NM, Sekar TV, et al. Polymer nanoparticles mediated codelivery of antimiR-10b and antimiR-21 for achieving triple negative breast cancer therapy. ACS Nano. 2015;9:2290–2302.

 PubMed Web of Science ®Google Scholar

Wang S, Zhang J, Wang Y, et al. Hyaluronic acid-coated PEI-PLGA nanoparticles mediated co-delivery of doxorubicin and miR-542-3p for triple negative breast cancer therapy. Nanomed Nanotechnol Biol Med. 2016;12:411–420.

 PubMed Web of Science ®Google Scholar

EbrahimianTaghavi M, Mokhtarzadeh S, Ramezani A, et al. Co-delivery of doxorubicin encapsulated PLGA nanoparticles and Bcl-xL shRNA using alkyl-modified PEI into breast cancer cells. Biochem Biotechnol. 2017;183:126–136.

 PubMed Web of Science ®Google Scholar

Farajzadeh R, Pilehvar-Soltanahmadi Y, Dadashpour M, et al. Nano-encapsulated metformin-curcumin in PLGA/PEG inhibits synergistically growth and hTERT gene expression in human breast cancer cells. Artif Cells Nanomed Biotechnol. 2017; Forthcoming. [9 p.]. doi: 10.1080/21691401.2017.1347879.

 PubMed Web of Science ®Google Scholar

Xiao B. Co-delivery of camptothecin and curcumin by cationic polymeric nanoparticles for synergistic colon cancer combination chemotherapy. J Mater Chem B Mater Biol Med. 2015;3:7724–7733.

 PubMed Web of Science ®Google Scholar

Jia M, Li Y, Yang X, et al. Development of both methotrexate and mitomycin C loaded PEGylated chitosan nanoparticles for targeted drug codelivery and synergistic anticancer effect. ACS Appl Mater Interfaces. 2014;6:11413–11423.

 PubMed Web of Science ®Google Scholar

Ma Y, Fan X, Li L. pH-sensitive polymeric micelles formed by doxorubicin conjugated prodrugs for co-delivery of doxorubicin and paclitaxel. Carbohydrate Polymers. 2016;137:19–29.

 PubMed Web of Science ®Google Scholar

Bao X, Wang W, Wang C, et al. A chitosan-graft-PEI-candesartan conjugate for targeted co-delivery of drug and gene in anti-angiogenesis cancer therapy. Biomaterials. 2014;35:8450–8466.

 PubMed Web of Science ®Google Scholar

Zhang R, Wang SB, Chen AZ, et al. Codelivery of paclitaxel and small interfering RNA by octadecyl quaternized carboxymethyl chitosan-modified cationic liposome for combined cancer therapy. J Biomater Appl. 2015;30:351–360.

 PubMed Web of Science ®Google Scholar

Deng X, Cao M, Zhang J, et al. Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer. Biomaterials. 2014;35:4333–4344.

 PubMed Web of Science ®Google Scholar

Yu X, Yang G, ShiY, et al. Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance. Int J Nanomedicine. 2015;10:7045–7056.

 PubMed Web of Science ®Google Scholar

Shali H, Shabani M, Pourgholi F, et al. Co-delivery of insulin-like growth factor 1 receptor specific siRNA and doxorubicin using chitosan-based nanoparticles enhanced anticancer efficacy in A549 lung cancer cell line. Artif Cells Nanomed Biotechnol. 2017; Forthcoming. [10 p.]. doi: 10.1080/21691401.2017.1307212.

 PubMed Web of Science ®Google Scholar

Shi S, Zhu X, Guo Q, et al. Self-assembled mPEG-PCL-g-PEI micelles for simultaneous codelivery of chemotherapeutic drugs and DNA: synthesis and characterization in vitro. Int J Nanomedicine. 2012;7:1749–1759.

 PubMed Web of Science ®Google Scholar

Guan X, Li Y, Jiao Z, et al. Codelivery of antitumor drug and gene by a pH-sensitive charge-conversion system. ACS Appl Mater Interfaces. 2015;7:3207–3215.

 PubMed Web of Science ®Google Scholar

Huang HY, Kuo WT, Chou MJ, et al. Co‐delivery of anti‐vascular endothelial growth factor siRNA and doxorubicin by multifunctional polymeric micelle for tumor growth suppression. J Biomed Mater Res. 2011;97:330–338.

 Google Scholar

Davoodi P, Srinivasan MP, Wang CH. Synthesis of intracellular reduction-sensitive amphiphilic polyethyleneimine and poly (ε-caprolactone) graft copolymer for on-demand release of doxorubicin and p53 plasmid DNA. Acta Biomaterialia. 2016;39:79–93.

 PubMed Web of Science ®Google Scholar

Lv S, Tang Z, Li M, et al. Co-delivery of doxorubicin and paclitaxel by PEG-polypeptide nanovehicle for the treatment of non-small cell lung cancer. Biomaterials. 2014;35:6118–6129.

 PubMed Web of Science ®Google Scholar

Kaneshiro TL, Lu ZR. Targeted intracellular codelivery of chemotherapeutics and nucleic acid with a well-defined dendrimer-based nanoglobular carrier. Biomaterials. 2009;30:5660–5666.

 PubMed Web of Science ®Google Scholar

Zheng C, Zheng M, Gong P, et al. Polypeptide cationic micelles mediated co-delivery of docetaxel and siRNA for synergistic tumor therapy. Biomaterials. 2013;34:3431–3438.

 PubMed Web of Science ®Google Scholar

Ma D, Lin QM, Zhang LM, et al. A star-shaped porphyrin-arginine functionalized poly(L-lysine) copolymer for photo-enhanced drug and gene co-delivery. Biomaterials. 2014;35:4357–4367.

 PubMed Web of Science ®Google Scholar

Xu W, Ling P, Zhang T. Polymeric micelles, a promising drug delivery system to enhance bioavailability of poorly water-soluble drugs. J Drug Deliv. 2013;2013:340415.

 Google Scholar

Debnath B , JashimUddin B, Maiti MD. Nanoparticle (NP) as a targeting drug delivery system to blood-brain barrier (BBB): a review. PharmaTutor. 2015;3:30–37.

 Google Scholar

Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75:1–18.

 PubMed Web of Science ®Google Scholar

Younes I, Rinaudo M. Chitin and chitosan preparation from marine sources. Structure, properties and applications. Marine Drugs. 2015;13:1133–1174.

 PubMed Web of Science ®Google Scholar

Liu M, Ji J, Zhang X, et al. Self-polymerization of dopamine and polyethyleneimine: novel fluorescent organic nanoprobes for biological imaging applications. J Mater Chem B. 2015;3:3476–3482.

 Web of Science ®Google Scholar