Drug carrier |
Stimulus response |
Drug |
Application |
Ref. |
Abraxane® (albumin–drug conjugate) |
– |
Paclitaxel |
Clinically approved for the treatment of breast cancer |
[14] |
NK105 (drug-loaded PEG–poly(aspartic acid) micelle) |
– |
Paclitaxel |
In clinical trials for the treatment of colon and stomach cancers |
[19] |
Doxil® (drug-loaded PEGylated liposome) |
– |
Doxorubicin |
Clinically approved for the treatment of recurrent ovarian cancer |
[22] |
ELP unimer |
Temperature-triggered aggregation |
– |
Increased accumulation in hyperthermia treated tumors in mice |
[34] |
Dextran–peptide–drug conjugate |
MMP cleavage of peptide linker for release of free drug |
Methotrexate |
Improved inhibition of tumor growth in subcutaneous murine models of human fibrosarcoma and glioblastoma |
[40] |
Poly(histidine)-β-PEG, poly(L-lactic acid)-β-PEG mixed micelle |
pH-triggered disassembly for release of free drug |
Doxorubicin |
Increased accumulation and improved efficacy in subcutaneous breast cancer tumors in mice |
[47] |
Pluronic® micelle |
Ultrasound-induced disassembly for release of free drug |
Doxorubicin |
Improved regression with ultrasound treatment in subcutaneous colon cancer tumors in mice in comparison to treatment with drug-loaded micelles alone |
[50] |
Oligoarginine–peptide–oligoglutamate conjugate |
MMP-2 cleavage of peptide linker for CPP activation |
– |
Increased accumulation compared with uncleavable controls in a variety of subcutaneously implanted tumor types in mice |
[65] |
PEG–poly(L-histidine), poly(L-lactic acid)–PEG–poly(L-histidine)–TAT mixed micelle |
pH-triggered display of TAT for CPP activation |
Doxorubicin |
Selective cellular uptake in slightly acidic conditions of pH 7.0 improved cytotoxicity in drug-resistant breast cancer cells |
[71] |
RGD-functionalized ELP diblock |
Temperature-triggered micelle assembly for polyvalent ligand display |
– |
Increased accumulation with hyperthermia-triggered micelle assembly in leukemia cells overexpressing αvβ3 integrin |
[77] |
Thiolated heparin nanogel |
Destabilization of disulfide bonds in reducing intracellular environment for free drug release |
Heparin |
Increased cytotoxicity by induction of apoptosis in melanoma cells as compared with free drug |
[84] |
ELP–drug conjugate micelle |
pH-triggered drug release in acidic endosomal compartment |
Doxorubicin |
Enhanced accumulation, increased MTD and improved regression of colon carcinoma tumors in mice |
[20] |
Poly(L-histidine)-based micelle |
pH-triggered protonation of histidine for endosomal disruption |
Doxorubicin |
Improved cytotoxicity of intracellularly released drug in doxorubicin-resistant ovarian carcinoma cells |
[92] |
Amidized poly(L-lysine)–drug conjugate |
pH-triggered charge reversal for nuclear targeting |
Camptothecin |
Nuclear localization of drug-enhanced cytotoxicity, compared with free drug, in adenocarcinoma cells |
[93] |
TPP-modified liposome |
– |
Ceramide |
Improved inhibition of tumor growth with mitochondrial targeting in a subcutaneous mouse model of mammary carcinoma tumors |
[94] |
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