Table 1.
Nanocarriers for autophagy modulators delivery.
| Autophagy Inducers/Inhibitors | Nano/Micro-Carriers | Co-Delivered Drug/siRNA | Disease | Targeting Agent | In Vitro/In Vivo | Major Outcomes | Refs |
|---|---|---|---|---|---|---|---|
| Rapamycin | Zain-lactoferrin micelles | Wogonin | Breast cancer | - | In vitro (MCF-7 breast cancer cells) and in vivo (Ehrlich ascites tumor animal model) | Inhibition of tumor growth with minimized side effects | [230] |
| Rapamycin | Hollow Fe₃O₄/Graphene Oxide Nanocomposites | - | - | - | In vitro (HepG2 cells) | High EE (84.92%), good stability and great cytotoxicity against HepG2 cells | [231] |
| Rapamycin | Berunda Polypeptides | - | Breast Cancer | - | In vivo (human MDA-MB-468 orthotopic breast cancer xenografts) and in vitro | Suppression of tumor growth and decreased viability of tumor cells | [232] |
| Rapamycin | Elastin-like Polypeptide NPs | Integrins | Breast cancer | - | In vivo (MDA-MB-468 breast tumor) | Inhibition of tumor growth in a higher level (3 folds) | [233] |
| Rapamycin | Immunoliposomes | - | Inflammatory disorder | anti-E-selectin | In vitro (activated endothelial cells) | Inhibition of endothelial cells migration and proliferation as well as inflammatory cytokines expression | [234] |
| Rapamycin | Polymer-lipid hybrid NPs | - | Hemangioma | - | In vitro (human hemangioma endothelial cells) and in vivo (female Balb/c mice) | Effective binding with HemECs and remarkable proliferation inhibition and decreased expression of angiogenic factors as well as decreased hemangioma volume, weight and microvessel density in in vivo | [235] |
| Rapamycin | Graphene oxides wrapped with PEGylated lipid bilayer | DOX | - | - | In vitro (MCF-7, MDA-MB-221 and BT474 cells) | Treatment and prevention of resistant cancer cells by up-regulating Bax, P21, P53, and caspase-3 and apoptosis induction | [236] |
| Rapamycin | Liposomes | Polypyrrol | Breast cancer | trastuzumab | In vitro (BT-474 cells) | Overcoming against drug resistance in breast cancer and higher therapeutic efficacy in breast cancer cells | [237] |
| Rapamycin | Lactose-wrapped calcium carbonate NPs | - | Cellular senescence | CD9 | In vitro (senescent cells) | Prevention of cellular senescence and improved proliferation of aged cells | [238] |
| Rapamycin | PEG-PCL NPs | - | Pulmonary arterial hypertension (PAH) | - | In vivo (rat model of PAH) | High accumulation of nanoparticles in lung, attenuation PAH development and also decreased systemic side effects compared to the free rapamycin | [239] |
| Rapamycin | Immunoliposomes | Paclitaxel | Breast cancer | Anti-HER2 | In vitro (HER2(+) breast cancer cells and triple negative cancer cells) and in vivo (nude mice with HER2(+) breast cancer cells) | High cytotoxicity due to enhanced uptake through HER2 binding and decreased tumor volume in vivo | [240] |
| Rapamycin | PLGA-PCL NPs | - | Breast cancer | - | In vitro MCF-7 and human lymphocyte cell (Jurkat cells) | Inhibition of cell proliferation in MCF-7 cells, suppression of cell growth in Jurkat cells and simultaneously, maintaining the bioactivity of rapamycin | [241] |
| Rapamycin | PLGA NPs | - | Venous neointimal hyperplasia | Pericardial patches | In vitro (human smooth muscle cells) and in vivo (male Wistar rats) | Sustained rapamycin delivery and subsequently, less neointimal hyperplasia, less smooth muscle cells proliferation and lower infiltrating cells and simultaneously, maintaining endothelization | [242] |
| Rapamycin | PEGylated liposomes | - | Cellular senescence | CD9 monoclonal antibody | In vitro (CD9 receptor-overexpressing cells) | Promotion of cell proliferation and reduction in the number of cells that express the senescence-associated-galactosidase, showing higher anti-senescence activity of CD9-targeted liposome compared to the free rapamycin and conventional liposomes | [243] |
| Rapamycin | PEO/PDLLA nanofibers | - | Glioblastoma | - | In vitro (U251 and U87 human glioblastoma cell lines) | Local sustained delivery of rapamycin, showing potential targeted delivery systems for glioblastoma treatment | [244] |
| Rapamycin | Polymeric NPs | Piperine | Breast cancer | - | In vitro (breast cancer cells) | Increased cellular uptake and bioavailability of rapamycin as well as decreased viability of cancer cells | [245] |
| Rapamycin | Lipid-polyaniline NPs | 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) | Cancer | - | In vitro (HeLa cells) and in vivo (HeLa tumor bearing mice) | High antiangiogenic effect and great cytotoxicity as well as decreased tumor growth | [246] |
| Rapamycin | Polymeric Micelle | Paclitaxel and 17-allylamino-17-demethoxygeldaramycin (17-AAG) | Cancer | - | In vitro (A549 cells) | Inhibition of A549 tumor growth, increased cytotoxicity and enhanced radiosensitizing effect | [247] |
| Rapamycin | poly(ethylene glycol)-shelled NPs | - | Aortic Aneurysm | - | In vivo (experimental aortic aneurysm in rat) | Remarkable inhibition of activities of matrix metalloproteinase and expression of inflammatory cytokines, showing their potential in targeting aortic aneurysm | [248] |
| Rapamycin | Acetalated b-CD (Ac-bCDs)-based NPs | - | Atherosclerosis | - | In vitro (smooth muscle cells) and in vivo (apoliproprotein E-deficient (ApoE) mice) | Decreased formation of atherosclerotic lesions, increased stability of plaques, decreased level of pro-inflammatory factors and suppression of mTORC1 | [249] |
| Rapamycin | Immunoliposomes | - | Breast cancer | Trastuzumab | In vitro (triple negative MDA-MB-231 and SKBR3cell lines) | High cytotoxicity against breast cancer cells | [250] |
| Rapamycin | Thermal sensitive liposomes | Indocyanine Green | - | - | In vitro (HeLa and HUVEC cells) and in vivo (HeLa cell bearing mice) | Great drug accumulation and cytotoxicity in vitro experiment and inhibited tumor growth in vivo with minimal side effects | [251] |
| Rapamycin | PLGA particles | Isoniazid and rifabutin | - | - | In vivo (infected mice) and in vitro (THP-1 human monocytes) | Stimulating more autophagy in infected macrophages, decreased bacterial burden in lung and spleen and inducing phagosome-lysosome fusion | [252] |
| Rapamycin | Liposomes | Paclitaxel | Breast cancer | - | In vitro (cancer 4T1 breast cancer cell line) and in vivo (4T1-tumor bearing mice) | Higher cytotoxicity against 4T1 cells and decreased tumor growth and viability in mice | [253] |
| Rapamycin | Human serum albumin NPs | Split luciferase reporter | Combined image guided monitoring the pharmacokinetics | [254] | |||
| Rapamycin | Solid Lipid NPs | - | - | - | In vitro (SH-SY5Y neuroblastoma cells) | High cellular uptake, sustained release and higher mTORC1 inhibition | [255] |
| Rapamycin | Biodegradable intraocular device | - | - | - | In vivo (New Zeland white rabbits) | Prolonged release, good stability and good ocular compatibility | [256] |
| Rapamycin | Lipid SAINT-O-Somes | - | - | Anti-VCAM-1 | In vitro (ABN12 and MPC-5 cell lines) | Remarkable inhibition of AB8/cell migration in targeted nanocarriers | [257] |
| Rapamycin | Nanoemulsions | - | - | - | In vitro (SKBR3 and Caco-2 cell lines) | Great cytotoxicity again SKBR-3 cell and good uptake by Caco-2 cells | [258] |
| Rapamycin | Microsphere | - | Kidney disease | - | In vivo (rat model of renal ischemic/reperfusion injury) | Lack of adverse effects, decreased macrophage infiltration and lower amount of myofibroblasts in kidney | [259] |
| Rapamycin | magnetic Fe3O4/carboxymethylchitosan NPs | - | Cancer | - | In vitro (liver cell line LO2 and human hepatocarcinoma cell line HepG2) | Sustained release of rapamycin, higher cytotoxicity against LO2 and HepG2 cells, increased cellular uptake and decreased damage to normal cells | [260] |
| Rapamycin | Nanoliposomal | CPT-11 | Brain tumor | - | In vivo (rodent orthotopic brain tumor xenografts) | Significant efficacy in increasing survival with minimal side effects | [261] |
| Rapamycin | Liposome | - | - | - | In vitro | High rapamycin encapsulation rate, good reproducibility and sustained release | [262] |
| Rapamycin | Aerosol treatment | 3-bromopyruvate | Lung cancer | - | In vitro (human non-small cell lung cancer (NSCLC)) and in vivo (mice with lung cancer0 | Remarkable inhibition of cell proliferation, decreased glycolytic activity, resulting in antitumor effect | [263] |
| Rapamycin | Porous silicon microparticles | - | - | - | In vivo (rabbit) | Great rapamycin loading, increased bioavailability and simultaneously, maintaining clear optical media and normal histology of retina | [264] |
| Rapamycin | Subcapsular microspheres | - | Chronic kidney disease | - | In vivo (ureter-obstructed rats) | Decreased intrarenal mTOR activity, over-expression of fibrotic genes, myofibroblast accumulation and T-lymphocyte infiltration and subsequently, successful inhibition of local fibrotic response | [265] |
| Everolimus | Chitosan NPs | - | Bronchiolitis obliterans syndrome (BOS) | - | In vitro (CD44-overexpressing mesenchymal cells) | Great properties in terms of average size (≤200 nm), good zeta potential (-30.9mV) and sustained release behavior as well as good uptake by mesenchymal cells | [266] |
| Everolimus | Polymeric NPs | Paclitaxel | Breast cancer | - | In vitro (MCF-7 and SKBR3 cells) | Synergistic effect on inhibiting the growth and decreasing viability of breast cancer cells | [267] |
| Everolimus | mPEGhexPLA nanocarriers | - | Autoimmune uveoretinitis (EAU) | - | In vivo (B10,RIII mice) | Significant decrease in EAU severity in both eyes and decreased secretion of IL-10 and CD4+ CD25+ FoxP3+ | [268] |
| 3-methyladenine | Metal-organic framework NPs | - | Cancer | - | In vitro (HeLa cells) and in vivo (nude mice) | Significant inhibition of autophagosome formation in HeLa cells and higher anti-tumor activity and inhibition of Beclin-1 and LC3 in mice | [269] |
| Cholorquine diphosphate | Metal-organic framework NPs | - | Cancer | Methoxy poly (ethylene glycol)-folate (FA-PEG) | In vitro (HeLa cells) | Remarkable inhibition of autophagosome formation and autophagy flux | [270] |
| Dactolisib | PLGA-PEG NPs | - | - | Anti-human E-selectin antibody | In vitro (TNF-activated endothelial cells) | High cellular uptake and great anti-inflammatory effects | [271] |