Recent advances in nanomaterial delivery systems to administer metformin for cancer therapy

Recently, an increasing number of studies and clinical trials have associated an antidiabetic drug metformin (Met) with reduced risks of cancer. Moreover, a potential of Met as an adjuvant to conventional therapies of cancer treatment has been highlighted as well. Nevertheless, the unfavorable pharmacological properties of Met can hinder its efficacy in cancer treatment. To overcome this challenge, drug delivery systems (DDSs) based on various nanomaterials (NMs) have been implemented to entrap Met with or without other therapeutic agents. This review will provide a detailed overview of Met entrapment in NMs for cancer therapy, which will include lipid-based NMs, polymer-based NMs, and inorganic-based NMs. These studies have highlighted the advantage of entrapping Met, achieving sustained drug release, enhanced accumulations of the drug at the tumor sites, as well as enhanced efficacy of therapies compared to their free drug forms. List of abbreviations ABCB1 ATP-binding cassette sub-family B member 1 ADP adenosine diphosphate AMP adenosine monophosphate AMPK AMP-activated protein kinase ATP adenosine triphosphate Bax Bcl-2-like protein 4 Bcl-2 B-cell lymphoma 2 Bup bupivacaine CD carbon dots CD24 − cluster of differentiation 24-negative CD3 + cluster of differentiation 3-positive CD4 + cluster of differentiation 4-positive CD44 cluster of differentiation 44 CD44 + cluster of differentiation 44-positive CD8 + cluster of differentiation 8-positive DDS drug delivery system DL drug loading DNA deoxyribonucleic acid Dox doxorubicin EE encapsulation efficiency EPR enhanced permeability and retention Flu fluvastatin sodium HD hydrogel HIF hypoxia-inducible factor His/ZIF-8 histidine/zeolitic imidazolate framework-8 IC 50 half-maximal inhibitory concentration IR775 infrared 775 heptamethine cyanine chloride dye IR780 infrared 780 heptamethine cyanine iodine dye Ki-67 Kiel-67 LP liposome Mc micelle Met metformin OXPHOS oxidative phosphorylation MSNP mesoporous SiO 2 nanoparticle mTOR mammalian target of the rapamycin NADPH Nicotinamide Adenine Dinucleotide Phosphate NF nanofiber NM nanomaterial NP nanoparticle NS nanosheet NT nanotube OCT1 organic cationic transporter 1 PD1 programmed cell death protein 1 PD-L1 programmed death-ligand 1 PEG poly(ethylene glycol) P-gp P-glycoprotein PLGA poly(lactic-co-glycolic acid) POLR2A RNA polymerase II subunit A PolyMet poly(metformin) RGD arginine-glycine-aspartic acid RNA ribonucleic acid ROS reactive oxygen species siRNA small interfering RNA Tween 80 poly(oxyethylene) 80 sorbitan monooleate