Table 4.
Different Lysosome-Targeted Nanoformulations Used for Therapy and Imaging Purpose Based on Autophagy and Non-Endocytic Uptake in Different Cancer Cell Types
| Nanoparticle Type and Size | Cellular Uptake Mechanism | In vitro/in vivo Models | Imaging/Therapy and Applications | References |
|---|---|---|---|---|
| Au–ZnO hybrid NPs decorated with cyclic RGD | Integrin receptor-mediated endocytosis | In vitro (HepG2 cells integrin positive) and HL7702 (integrin negative) cells | ZnO mediated ROS generation, LMP-dependent apoptosis | [240] |
| HApt grafted Au NS (410±10 nm) | HER 2 mediated endocytosis | In vitro (SK-BR-3 cells) | HER 2 inhibition, lysosomal degradation cell cycle arrest (Go/G1), apoptosis | [241] |
| Nucleic acid decorated Au NPs | – | In vitro (HeLa cells) | Acid-sensitive DOX delivery | [242] |
| Lyso-Ru-NO@FA@C–TiO2 NPs | Folate receptor mediated endocytosis | In vitro HeLa cells (FA positive) & MCF-7 (FA negative) | NO delivery (ΦNO=0.0174±0.002 mol E−1) and PDT (ΦΔ=0.23–0.28) at 808 nm irradiation | [243] |
| NGO-PEG-BPEI NPs | Energy-dependent endocytic pathway | In vitro (HeLa cells) | PDT (Cholin Ce6) | [244] |
| Gastrin grafted magnetic NPs (8.7±1.6 nm) | – | In vitro, INRIG9-CCK2R cells | PTT and ROS production (Fenton reaction), caspase 1, and cathepsin B dependent apoptosis | [245] |
| L-tyrosin and poly(ester-urethane) based NPs (100±10 nm) | Energy-dependent endocytosis | In vitro (MCF-7 and HeLa cells) | Thermo and lysosomal esterase responsive DOX and CPT drug delivery | [246] |
| Ru-CD-RGD NPs (61 nm) | Integrin receptor mediated endocytosis | In vitro (U87MG cells (Integrin positive) MCF-7 cells | ROS production, caspase dependent apoptosis | [247] |
| Iron oxide-based MG-IONP-DY647 NPs | β-arrestins, clathrin-pits, and dynamin dependent endocytosis | In vitro, HEK293 (CCK2R positive) cells | Lysosomal dependent apoptosis | [248] |
| FA-conjugated FA-SPIONs (67 nm) | Folate receptor-mediated endocytosis | In vitro and in vivo (MCF-7 cells) | MRI imaging and acid sensitive DOX delivery | [249] |
| Biotinylated chitosan CaCO3 NPs (200 nm) | Biotin receptor mediated endocytosis | In vitro (MCF-7/ADR DOX resistant and HeLa DOX non-resistant cells | Acidic pH-dependent DOX and TQR (P-gp inhibitor) delivery | [250] |
| Meso-silica based MSNs-siRNA@DOX-PEG-FA NPs | Folate receptor mediated endocytosis | In vitro (MCF/ADR cells), In vivo (MCF/ADR | Acidic pH-sensitive DOX release, and SiRNA delivery | [251] |
| Fe3O4/CPs based NPs (150 nm) | Endocytosis | In vitro (HepG2 cells), In vivo (H22 tumor xeno-graft, i.v. administration) | pH-dependent Zn2+ ion release, ROS production and LMP triggered apoptosis | [252] |
| Bis-styryl BODIPY & DSPE-mPEG5000 NPs | – | In vitro (A549 cells) and in vivo (A549 tumor xenograft) | pH-dependent PDT (730 nm irradiation) | [253] |
| Fluo-Mor NPs | – | In vitro (HT-20 cells) | pH-dependent PDT (ΦΔ=0.65 at pH 3, 365 nm irradiation) | [254] |
| Lysosomal escaping and lysosomal toxicity nanoformulations | ||||
| NaYF4:Eu3+ NPs NY50 (50 nm) NY200 (200 nm) | – | In vitro (BMSC cells) | LMP, lysosomal swelling, cathepsins B and D, ROS generation leads to necrosis | [255] |
| SiRNA loaded nanogels (siNGs) incubated with CADs | Endocytosis | In vitro (H1299 cells) | siRNA delivery | [256] |
| S-NP/DNA NPs | Endocytosis | In vitro (HeLa cells) | DNA delivery | [257] |
| pH-responsive R-P@MSN–DTX NPs | Endocytosis | In vitro (HeLa cells), In vivo (HeLa tumor-bearing mice) | pH Responsive DTX delivery | [258] |
| INF-7 peptide modified magnetic NPs | – | In vitro (Caco-2Luc cells) | siRNA delivery | [259] |
| Gd2O3@albumin NPs (GA-NP) conjugated with Ce6 PS (10.1 nm) | – | In vitro (4T1 cancer cells), In vivo (4T1 tumor-bearing mice) | MRI-guided PDT and PTT (ФΔ=0.1, temperature rise at tumor ∼13°C) | [260] |
| Unimolecular NPs | EGFR-mediated endocytosis | In vitro (MDA-MB-468 cells) | pH/Redox dual sensitive siRNA siRNA delivery | [261] |
| EGF-HMSNs-5-FU (120 nm) | EGFR mediated endocytosis | In vitro (SW480/ADR cells) MCF-7 cells (integrin negative) | 5-FU delivery | [262] |
| VM-RGD-NPs (2.75 nm) ZnO NPs | Endocytosis | In vitro (BEL-7402/MDR tumor cells), In vivo (BEL-7402/MDR xenograft nude mice) In vitro (SHSY5Y cells) | Verapamil and mitoxantrone delivery ROS generation by zinc ions delivery | [263] |
| Nanolipoplexes (Nx NPs) | Endocytosis | In vitro (THP-1 macrophages & HIV TZM-bl cells) | siRNA delivery | [264] |
| Autophagy and non-endocytic uptake nanoformulations | ||||
| Multiwall carbon nanotubes (MWCNT) | – | In vitro (RAW264.7 macrophages) | Toxic effects due to increased autophagy, the fusion of lysosomes and autophagosomes | [265] |
| Arginine functionalized gold NPs as a nanoparticle-stabilized nanocapsule (NPSC) | Non-endocytic uptake pathway | In vitro (HEK293 cells) | Delivery of siRNA, Depleted the PLK1 expression in cancer cells | [266] |
| Gold nanoparticles (AuNPs) and HIV-1 Tat CPPs. | Direct translocation through the cell membrane (non-endocytic pathway) Non-endocytic pathway | In vitro (human bronchial epithelial cells) | The shape of the cationic object is crucial in the translocation of the cell membrane | [267] |
| Single-walled carbon nanotubes (SWNT) | Endocytosis | In vitro (CRND8 glial cells) | Reversal of lysosomal proteolysis deficiency and restored the normal mTOR signaling | [268] |
| Silica NPs (SiNPs) | Endocytosis | In vitro (L-02) and HepG2 cells | Induced autophagy and inhibited the autophagic flux | [269] |
| QD decorated with arginine-based cell-penetrating poly (disulfide)s linkage (CPD-QD) NPs | Direct translocation | In vitro, Drosophila S2 cells | Delivery of QDs and delivery of GFP or anti-GFP nanobodies | [270] |
| Palladium nanoparticles (PdNPs) (20 nm) | Endocytosis | In vitro (HeLa cells) | Autophagic flux blockade and cell death | [271] |
| Photoactivated nanoparticles (paNps) | – | In vitro, fatty acid–treated INS1 rat- pancreatic beta cells | Reversal of normal lysosomal acidic levels under UV photoactivation | [272] |
| Graphene oxide NPs and acid-functionalized single-walled carbon nanotubes | – | In vitro (Mouse peritoneal macrophages) | Toxic effects due to the induced autophagy | [273] |
| Gold nanospheres | Endocytosis | In vitro (HeLa cells) | Trigger more autophagosome accumulation | [274] |
| Cobalt oxide (Co3O4) NPs | Non-endocytic pathway | In vitro (Xenopus laevis oocytes) | Calcein-fluorescence quenched after non-transfected (NT) Calcein- injected oocytes exposed to (Co3O4) NPs | [275] |
| Arginine-terminated QD NPs | Direct translocation | In vitro (HeLa and HT22 cells) | Delivery of DQs | [276] |