Table 2.

Summary of polymer-drug conjugates efficacy on breast cancer in vitro and in vivo.

Polymer-Drug Conjugates	Carrier/ Monomers Used	Drugs	Biological Outcomes	Molecular Design	Reference
N-(2-hydroxypropyl methyl) acrylamide copolymer-gadolinium-paclitaxel-Cyanine5.5	N-(2-hydroxypropyl methyl) acrylamide	Paclitaxel	Mode of administration in vivo: Intravenous. Prolonged residence time, high accumulation of the conjugate at the tumor site. Inhibition of proliferation and induced apoptosis of the 4T1 murine breast cancer cells.	The amphiphilic block polymer was prepared via a two-step Reversible Addition-Fragmentation chain Transfer polymerization and self-assembled into a nanoparticle. Enzyme-sensitive tetrapeptide linker was used as a spacer in the conjugate to promote the degradation of high molecular weight conjugates into low molecular weights with the release of the drug in the cancer microenvironment.	[111]
Hyaluronic acid-Doxorubicin-Gemcitabine	Hyaluronic acid	Doxorubicin and gemcitabine	Mode of administration in vivo: Intravenous and subcutaneous. The conjugates loaded with both drugs were active in inhibiting the formation of an orthotopic, aggressive 4T1 tumor model in vivo when compared to individual drugs and the polymer-conjugates loaded with a single drug.	The amine on gemcitabine was conjugated to the carboxylic acid on amino acids to form a prodrug. The prodrug was conjugated to hyaluronic acid via carbodiimide chemistry. Doxorubicin was conjugated to hyaluronic acid via carbodiimide chemistry.	[112]
PEG-folic acid-trastuzumab	Polyethylene glycol	Folic acid and trastuzumab	The in vitro cellular uptake of the prodrugs conjugated with both drugs was high when compared to the non-targeted polymeric prodrugs. The conjugate displayed apoptosis of 80% with enhanced tumor regression in vivo.	The copolymer was prepared by ring-opening polymerization of PEG and lactide followed by isomerization polymerization of the triblock copolymer and 2-hydroxyethyl disulfide using dibutyltin dilaurate as a catalyst.	[113]
N-(2-hydroxypropyl) methacrylamide -Doxorubicin	N-(2-hydroxypropyl) methacrylamide	Doxorubicin	Mode of administration in vivo: Intravenous. The conjugate exhibited reduced glycolysis, increased apoptosis, and reduced degree of phospholipids when compared to the free doxorubicin. The in vivo studies on the 4T1 breast tumor mouse model using the conjugate revealed a high reduction in the growth of tumors when compared to free DOX-treated mice.	DOX was incorporated into the carriers, and enzyme-sensitive tetrapeptide linker was used as a spacer in the conjugate to promote the degradation of high molecular weight conjugates into low molecular weights with the release of the drug in the cancer microenvironment.	[114]
Poly-l-glutamic acid-Doxorubicin-Aminoglutethimide	Poly-l-glutamic acid	Doxorubicin and aminoglutethimide	Mode of administration in vivo: Intravenous. The conjugates displayed enhanced tumor cell death and inhibited tumor-related activities. However, the conjugates containing [N-ε-maleimidocaproic acid hydrazide] moiety displayed a higher survival rate and pro-apoptotic activity, lower anti-apoptotic signals, and inhibition of metastasis.	The conjugates loaded with Dox and aminoglutethimide were prepared with pH-sensitive linkers—hydrazine moiety or complex EMCH [N-ε-maleimidocaproic acid hydrazide] moiety—for the release of Dox in the tumor microenvironment.	[115]
Polyethylene glycol -Doxorubicin (PEG-DOX)	Polyethylene glycol	Doxorubicin	Mode of administration in vivo: Intraductal. Increased molecular weight and decreased branching prolonged the retention of the drug in the mammary gland after administration.	Dox was conjugated to PEG polymers with varied molecular weights (5, 10, 20, and 40 kDa) and architectures of linear, four-arm, and eight-arm.	[116]
Poly(l-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-Mpeg-PTT	Poly(l-glutamic acid)-g-methoxy poly(ethylene glycol)	Podophyllotoxin	The conjugates decreased the hemolytic activity of the drug. The conjugates’ antitumor activity against MCF-7/ADR xenograft tumors was high, with a tumor suppression rate of 82.5%.	The drug was conjugated into poly(l-glutamic acid)-g-methoxy poly(ethylene glycol) (PLG-g-mPEG) via ester bonds.	[117]
Polyamidoamine-Pamidronate-Platinum (PAMAM-PAM-Pt)	Polyamidoamine	Pamidronate and platinum	The conjugates were not toxic when compared to the free drugs.	The conjugates were synthesized by aqueous phase Michael-addition polymerization reaction.	[118]
Beta-cyclodextrin- Polyethylene glycol-Folic Acid-doxorubicin (β-CD-PEG-FA-DOX)	Polyethylene glycol, Beta-cyclodextrin	Doxorubicin	Mode of administration in vivo: Intravenous. Reduced tumor volume, no systemic toxicity, and cardiotoxicity.	Beta-cyclodextrin (β-CD)-based carrier was composed of β-CD, polyethylene glycol, and folic acid for enhanced drug delivery.	[119]
Methoxy Polyethylene glycol-Polylactic acid-Doxorubicin (mPEG-b-PLA-g-DOX)	Polyethylene glycol, Polylactic acid	Doxorubicin	The cytotoxicity studies showed the cytocompatibility of polymeric carriers to MCF-7 breast cancer cell lines with the viability of cells greater than 80%.	The conjugates were prepared by ring-opening polymerization and condensation followed by click reaction. The carriers were grafted with a triazo group. Doxorubicin was modified with cyclooctyne and conjugated to the carriers by strain-promoted alkyne-azide cycloaddition click reaction.	[120]
poly(oligoethylene glycol acrylate) (POEG-VBC-DOX)	poly(oligoethylene glycol acrylate)	Doxorubicin	Mode of administration in vivo: Intravenous. Synergistic anti-tumor and anti-metastasis activity in vitro and in vivo.	DOX was incorporated POEG-VBC backbone.	[121]
N-(1,3-dihydroxypropan-2-yl) methacrylamide-Doxorubicin	N-(1,3-dihydroxypropan-2-yl) methacrylamide	Doxorubicin	Extended blood circulation time with an elimination half time of 9.8 h. High accumulation in the tumors and improved in vivo therapeutic efficacy against 4T1 xenograft tumors compared to the free DOX. Tumor inhibition was via inhibition of cell proliferation and antiangiogenic effects.	The conjugates were synthesized by RAFT polymerization, followed by drug conjugation.	[122]
Polymalic acid-Trastuzumab	Polymalic acid	Trastuzumab	Mode of administration in vivo: Intravenous. Enhanced tumor growth inhibition.	Polyethylene glycol (PEG) and poly (β-l-malic acid)-drug conjugates were prepared by covalently incorporating anti-HER2/neu peptide.	[123]
Polyamidoamine-Procaine-Platinum-Alendronate	Polyamidoamine	Procaine, Platinum (II), Alendronate	Selective inhibitory effects of the conjugates towards the cancer cell lines.	The conjugates were synthesized by aqueous phase Michael-addition polymerization reaction.	[124]
Polyamidoamine-Procaine-Pt-Alendronate	Polyamidoamine	Ferrocene, Pt (II)	Selective inhibitory effects of the conjugates towards the cancer cell lines.	The conjugates were synthesized by aqueous phase Michael-addition polymerization reaction.	[125]