Table 3.
Drug‐delivery system conjugates
| Drug | Status | Delivery system | Model | Efficacy/Potency |
|---|---|---|---|---|
| Tamoxifen | In vivo | Naringen (P‐gp efflux inhibitor) | MCF‐7 cells and female Wistar rats | The conjugate showed 22‐fold increased cytotoxicity compared to tamoxifen or the combination.95 |
| Tamoxifen | In vivo | Chitosan‐stearic acid‐based polymeric micelles | MCF‐7 cells | Enhanced cytotoxicity and modified pharmacokinetic profiles.109 |
| Tamoxifen | In vitro | Trans‐2‐phenylcyclopropylamine | Lysine‐specific demethylase 1‐triggered controlled release | No toxic effect on normal cells.85 |
| Tamoxifen | In vitro | Glucosamine‐porphyrin | MCF‐7 cells | Works through necrosis/apoptosis pathways.4 |
| Tamoxifen | In vivo | Bile (cholic) acid | 4T1 in vivo model | More potent than tamoxifen.104 |
| Tamoxifen | In vitro | Thiol‐polyethylene glycol gold nanoparticle | MCF‐7 cells | The conjugate showed 2.7 folds higher potency than tamoxifen with less cytotoxicity to cancer cells.28 |
| Tamoxifen | In vitro | Pyropheophorbide | MCF‐7 cells | Showed light‐specific cytotoxicity35 |
| Gefitinib | In vitro | Polyarginine peptoids | MDA‐MB‐468, NME, and LM1 cell lines | NArg‐based conjugate blocked STAT3 phosphorylation without affecting ERK1/27 |
| Mitoxantrone | In vivo | Folic acid‐tocopheryl polyethylene glycol | MCF‐7 xenografted mice | MTO‐FMCT showed improved cellular uptake with higher MCF‐7 cytotoxicity. MTO‐FMCT showed higher potency to reduce MCF‐7 cell viability compared to MTO alone43 |
| Polymeric doxorubicin | In vivo | Aminopropyltriethoxysilane‐modified porous silicon particles | MDA‐MB‐231 and 4T1 mouse models of metastatic breast cancer | Nanoparticles showed enhanced efficacy with functional cures in 40%‐50% of treated mice120 |
| Doxorubicin | Retrospective Clinical Study | Pegylated liposomal nanoparticles | Stage I‐III triple‐negative breast cancer patients | Adjuvant chemotherapy was as effective as conventional chemotherapy with reduced toxicity66 |
| Paclitaxel (Abraxane®) | FDA approved | Albumin‐bound nanoparticles | Clinical trials on metastatic breast cancer | Abraxane® showed superior efficacy and reduced toxicity compared with paclitaxel39 |
The uptake of nanoparticles by a tissue depends on the hydrophobicity of that nanoparticle. For example, nanoparticles deposited in certain organs such as the liver, spleen, and reticuloendothelial system correlate positively with the increasing hydrophobicity of the polymer.37 Although several nanoparticle‐based drug delivery systems have been developed, only albumin‐bound paclitaxel nanoparticle (Abraxane®) was approved by FDA for metastatic breast cancer and nonsmall cell lung carcinoma.69 Nanotechnology can also be effectively used in breast cancer treatment. Nanoparticle conjugates may show increased potency by penetrating the cells by endocytosis instead of the diffusion method used for a single drug.28 This could be a mechanism to avoid efflux by drug transporters such as P‐glycoprotein.14 In a phase III clinical trial, paclitaxel nanoparticles bonded with albumin showed superior efficacy and safety compared to paclitaxel dissolved in castor oil.39 Furthermore, doxorubicin linked with poly(L‐glutamic acid) by a pH‐sensitive cleavable linker showed enhanced efficacy in MDA‐MB‐231 and 4T1 metastatic breast cancer mouse model.120