Table 2.
NO Nanomedicines for Tumor Therapya
| Nanomedicine | NO donor | Release condition | Working mechanism of NO | Refs |
|---|---|---|---|---|
| RBS-T-UCNPs | Roussin’s black salt (RBS) | 808 nm laser irradiation | Sensitizing chemotherapy by reducing tumorigenic ability: inhibiting cancer stem-like cells and mammosphere formation ability, reducing CD44+ / CD24− subsets. | 184 |
| α-CD-Ce6-NO NPs | α-CD-NO | GSH | Sensitizing PDT: depleting intracellular GSH, relieving hypoxia at tumor sites, and ONOO− generation to enhance ROS reactivity. | 69 |
| RBS-UCNPs | RBS | 808 nm laser irradiation | Sensitizing chemotherapy: High NO concentration kills cancer cells; low NO concentration reduces P-gp level to overcome MDR. | 30 |
| NanoNO | DNIC [Fe(μ-SEt)2(NO)4] | Physiological condition | Sensitizing chemotherapy: gradient NO generation efficiently reprograms tumor vasculature and microenvironments to improve chemotherapy | 42 |
| NMOF−SNO | R-SNO | 808 nm laser irradiation | Sensitizing PTT: NO releasing to enhance PTT efficiency | 185 |
| DN@MSN | R-SNO | Natural release | Sensitizing chemotherapy: NO activating MMP-1 and MMP-2, promoting DOX delivery to more deep tumour tissues | 47 |
| Peptide-HMSN-LA | L-Arg | ROS | NO direct oxides proteins | 81 |
| photoNORM/UCNP | Metal-NO | 794 nm laser irradiation | Low dose reduces HIF-1a, and high doses are cytotoxic | 186 |
| PTNGs | R-SNO | 808 nm laser irradiation (Photothermal) | Sensitizing chemotherapy: NO reverses MDR by inhibiting Pgp expression | 187 |
| GCZ@M | nitrosoglutathione (GSNO) | Ultrasound irradiation | Sensitizing SDT: ONOO− generation, relieving tumour hypoxia | 188 |
| IDDHN | 2-(Nitrooxy)acetic | 808 nm laser irradiation (Photothermal) | Sensitizing chemotherapy: NO improves the EPR effect | 189 |
| L-Arg-HMON-GOx | L-Arg | H2O2 | Starving-like/NO for synergistic cancer therapy | 190 |
| BNN-Bi2S3 | Bis-N-nitroso compounds | 808 nm laser irradiation | NO impairs the autophagic self-repairing ability of tumor cells in situ | 76 |
| PFTDPP-SNAP NPs | R-SNO | 808 nm laser irradiation (Photothermal) | Sensitizing PTT: NO generation enhances PTT efficiency | 191 |
| Lip-SNAP | S-nitroso-N-acetylpenicillamine | GSH | NO induces stromal depletion for improved nanoparticle penetration | 192 |
| S–NO NPs | Aryl N-nitrosamine | 808 nm laser irradiation (Photothermal) | NO release activates photothermal agent for synergistic tumor treatment | 193 |
| QM-NPQ@PDHN | NPQ | Glutathione S-transferases π | Specific, high-efficacy, and low-toxic patocellular carcinoma therapy | 194 |
| AL-SISIN-1 | SISIN-1 | Physiological conditions | Inhibiting tumour metastasis by inducing cytotoxicity preferentially on tumour cells in lymph nodes | 195 |
| iCPDN | R-SNO | GSH | Sensitizing chemoimmunotherapy: Reversing DOX resistance and enhancing antitumor immune responses by reprogramming the tumor microenvironments. | 196 |
| WB@hydrogel | BNN6 | 1064 nm laser irradiation (photothermal) | Anti-angiogenesis and tumor microenvironment reprogramming: activating wild type p53 expression, alternating pro-angiogenic TME to anti-angiogenic TME. | 80 |
| pPTX/pCD-pSNO | R-SNO | Redox conditions | Sensitizing chemoimmunotherapy: Enhancing dendritic cell activation, T cell expansion, cytotoxicity, and immunogenic cell death, | 197 |
| TPE-RSNO micelles | R-SNO | H2O2 | Reducing P-gp expression, reversing MDR, RNS | 198 |
| FZ-SS-FZ@FA NPs | phenylsulfonylfuroxan | GSH | Upregulating p53 and cleaved caspase-3 proteins | 199 |
| Ce6/PDE5-i@FHMON-O2 | _ | DE5-inhibited PDE5 pathway to upregulate eNOS | RNS helps ROS to evade the hypoxia-induced resistance to ROS-based antitumor | 200 |
| NPSD-IR | NTC | GSH | Sensitizing chemotherapy: inhibiting Pgp expression to overcome MDR | 25 |
| PIH-NO | R-SNO | Ultrosound | ONOO− generation to enhance SDT, promote the maturation of dendritic cells, and increase immune cells infiltration | 201 |
| PtR/CPG | L-Arg | H2O2 | Enhancing anticancer chemoimmunotherapy: NO can trigger immunogenic cell death to produce tumor-associated antigens | 202 |
| HFC/DTX/aPD1 | L-Arg | The environment of cancer cells | Promoting anticancer chemoimmunotherapy | 203 |
| NO-DOX@PDA-TPGS-Gal | N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine (BNN) | 808 nm laser irradiation (photothermal) | Enhancing chemo−photothermal therapy: inhibiting P-gp -the related efflux of DOX | 204 |
| S1P/JS-K/Lipo | JS-K | Glutathione S-transferases | Promoting glioblastoma multiforme cell death | 20 |
| CMH-OBN | Benzofuroxan | GSH | ONOO− generation enhances PDT/PTT/immunotherapy | 205 |
| Alb-PLP/NO NPs | Diazeniumdiolate | Physiological conditions | Enhancing tumor penetration and inhibiting melanoma. | 206 |
| P@BDOX/β-lapachone-NO-NPs | R-O-NO2 | GSH | Overcoming chemo-resistance and enhancing the efficacy of HIFU in combination with chemotherapy | 207 |
| SPNAPt/NO | R-O-NO | GSH | ONOO− generation down-regulates glutathione reductase (GR) and xeroderma pigmentosum group A | 32 |
| LPFe3O4 NPs | L-Arg | iNOS | NO enhances immune therapy | 208 |
| BPNs-Arg-GOx@MnO2 | L-Arg | H2O2 | NO activates matrix metalloproteinases to degrade the dense extracellular matrix | 209 |
| UC-ZIF/BER | R-O-NO | NIR irradiation to UV by upconversion | NO turns on the ryanodine receptors for Ca2+ elevation to achieve Ca2+-initiated cancer therapy | 210 |
| Artificial microbots (AMBs) | L-Arg | iNOS and ROS | Regulating vasodilation and invasion to promote drug release to solid tumors | 211 |
| HFLA-DOX | L-Arg | H2O2 | Promoting deep drug penetration and reversal of MDR in cancer chemotherapy. | 212 |
| L-Arg@Ce6@P NPs | L-Arg | H2O2 | Inhibiting mitochondrial respiration | 213 |
| HA@MOF/D-Arg | D-Arg | H2O2 | Down-regulating HIF-1α to alleviate tumor hypoxia for sensitizing radiotherapy | 214 |
| ArgCCN | L-Arg | H2O2 | High concentration NO induces cancer cell apoptosis | 215 |
| RBCm/PAAVSNO/IR1061 + 1-MT NPs | R-S-NO | Heat and pH | NO normalizes tumor vessels | 216 |
| NO-NCPs | DETA NONOates | pH and photoacoustic | ONOO− generation to damage lysosome, mitochondria, and DNA | 86 |
| CuS-PEI/NO-TPP | Diazeniumdiolate | 1064 nm laser irradiation (photothermal) | Inhibiting heat shock proteins expression | 74 |
| GMOF-LA | L-Arg | H2O2 | NO sensitizes PDT | 217 |
| ZGO-Mn-RBS | Roussin’s black salt | X-ray excitation | depth-independent NO-releasing strategy for gas-sensitized therapeutic applications. | 218 |
| Ptx@AlbSNO | R-SNO | GSH | Enhancing immune cell infiltration into tumor microenvironments. | 219 |
| BSA-IRLA@RVs-RGD | L-Arg | ROS | Inhibiting cancer-associated platelet activation and disrupting tumour vascular barriers | 220 |
| Au@SiO2-SNO/PEG/TPP | R-SNO | 808 nm laser irradiation (Photothermal) | Activating MMPs to break collagen fibers to enhance the cellular internalization | 221 |
| α-CD-DOX-NO-DA NPs | R-SNO | GSH | NO facilitates mitochondrial membrane permeabilization and downregulates ATP level and inhibits pgp to reverse MDR | 222 |
| Micellar NO@HMs | NONOate | pH | ONOO− generation sensitizes radiotherapy of hypoxia tumor | 50 |
| DM1-NO-NPs | R-SNO | X-ray irradiation | ONOO− causes DNA and lipid damage to sensitize radiotherapy. | 223 |
| SNO-HSA Dimer | R-SNO | Physiological conditions | NO augments the EPR effect to promote drugs to the tumors. | 224 |
| DPP-NF NPs | 4-Nitro-3-Trifluoromethylaniline | 660 nm laser irradiation. | NO directly damages DNA, and inhibits the expression of HIF-α to enhance PDT efficiency | 225 |
| Lyso-Ru-NO@FA@C-TiO2 | R-NO | 808 nm light irradiation | Lysosome-targeted NO delivery to enhance PDT | 226 |
| PpRE@PEG-PpIX NPs | R-Fe(NO)2 | 637 nm laser irradiation | Reversing MDR and overcoming hypoxia to enhance PTT. | 227 |
| Ce6-loaded NO-mannan | R-O-NO2 | GSH | NO prompts vessel-relaxing and hypoxia relief | 228 |
| N-GQDs@Ru-NO@Gal | R-NO | 808 nm light irradiation | NO enhances PTT | 229 |
| CPNs | R-O-NO2 | GSH | ONOO− and NO inhibit Pgp expression to reverse MDR | 33 |
| L-Arg@PCN@Mem | L-Arg | ROS | NO overcomes hypoxia to sensitize PDT | 70 |
| P(IR/BNN6/AIPH)@Lip-RGD | BNN6 | 1064 nm laser irradiation (Photothermal) | Synergistic NO and alkyl radical action | 230 |
| Fe(II)-BNCP | BPDB | GSH | Synergistic NO and chemodynamic therapy | 89 |
| ADAu@CuS YSNPs | L-Arg | ROS | Inhibiting P-gp expression to reverse MDR | 29 |
| IPO-NO | R-SNO | 808 nm laser irradiation (Photothermal) | Low NO concentration increases the EPR effect and high concentration directly kills the tumors. | 231 |
| IMesNO/DOX@MCs | R-NO | HIFU irradiation | Accelerating drug accumulation in tumor | 232 |
| PV-TS | Sodium nitroprusside dihydrate | GSH | NO inhibits cellular respiration to relieve tumor hypoxia | 65 |
| NO-M@DOX | R-O-NO2 | GSH | NO reverses MDR to enhance chemotherapy | 233 |
| N-GQDs@Ru-Cl@TPP | R-NO | 808 nm light illumination | NO enhances PTT | 78 |
| M@BPAG | L-Arg | H2O2 | Reprogramming the tumour immune microenvironment and significant synergistic antitumor effect | 234 |
| AI-MPHA NCs | L-Arg | ROS | NO sensitizes PTT | 235 |
| PNOC-PDA/DOX | R-SNO | 808 nm laser irradiation (photothermal) | NO reverses MDR to sensitize PTT and chemotherapy | 34 |
| RBS-T-SCNPs | Roussin’s black salt | X-ray irradiation | ONOO−-generation directly damages DNA and downregulates the DNA-repair enzyme | 52 |
| HMs | DETA NONOate | pH | NO inhibits P-gp expression to reverse CPT MDR. | 31 |
| PEG-USMSs-SNO | R-SNO | X-ray irradiation | NO sensitizes radiotherapy of hypoxia tumor | 55 |
| P-lapa-Fc | L-Arg | ROS | ONOO− generation enhances tumor therapy | 64 |
| UMNOCC-PEG | R-SNO | pH | RNS generation enhances PDT/CDT | 90 |
| mCuMNO | S-nitrosoglu-tathione | Cu+ | Interrupting the interaction between platelets and circulating tumor cells and enhancing CDT | 236 |
| T-NPCA/NO | R-SNO | GSH | ONOO− promotes mitochondrial membrane permeabilization | 237 |
RBS-T-UCNPs, Roussin’s black salt-upconversion nanoparticles; α-CD-Ce6-NONPs, α-cyclodextrin-chlorin e6-NO nanoparticles; NMOF-SNO, nanoscale metal-organic framework-S-Nitrosothiol; DN@MSN, doxorubicin-NO-Mesoporous silica nanoparticles; Peptide-HMSN-LA, Peptide-hollow mesoporous silica nanoparticles-L-Arg; photoNORM/UCNP, photochemical precursor of NO-upconversion nanoparticles; PTNGs, phototriggered NO nanogenerators; GCZ@M, GSNO/Ce6@ZIF-8@Cytomembrane; IDDHN, intelligent nanoparticle; L-Arg-HMON-Gox, L-Arg-hollow mesoporous organosilica nanoparticle-glucose oxidase; BNN-Bi2S3, bis-N-nitroso compounds-bismuth sulfide; PFTDPP-SNAP NPs, semiconducting polymer-s-nitrosothiol groups nanoparticles; Lip-SNAP, SNAP loaded liposomes; S–NO NPs, N-nitrosamine nanoparticles; QM-NPQ@PDHN, fluorogen QM-2-O2-(2,4-dinitro-5-{[2-(β-d-galactopyranosyl olean-12-en-28-oate-3-yl)-oxy-2-oxoethyl] piperazine-1-yl}- phenyl) 1-(methylethanolamino)diazen-1-ium-1,2-dilate-PEGylated disulfide-doped hybrid nanocarriers; AL-SISIN-1, N-((2-pyridin-2-yldisulfanyl)ethoxyl)carbonyl-3-morpholinosydnonimine; iCPDN, poly(amidoamine)-Doxorubicin-NO; WB@hydrogel, WO2.9-N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine@hydrogen; BNN6, N,N′-di-sec-butyl-N,N′-dinitroso-1,4-phenylenediamine; pPTX/pCD-pSNO, polymerized paclitaxel-nitric oxide-incorporated polymerized β-cyclodextrin; TPE-RSNO micells, S-nitrosothiol-functionalized tetraphenylethene; FZ-SS-FZ@FA NPs, phenylsulfonylfuroxan nanoparticles; Ce6/PDE5-i@FHMON-O2, photocleaved O2-released nanoplatform; NPSD-IR, IR-780-Doxorubicin NO nanoparticles; PIH-NO, perfluorodecalin-IR780-human serum albumin- NO; PtR/CPG, cis-platinum-L-arginine/ Cytosine-phosphorothioate-guanine; HFC/DTX/aPD1, heparin-folate-cy5.5/l-arginine/ docetaxel/anti-PD-1; S1P/JS-K/Lipo, sphingosine-1-phosphate/ O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate/liposome; JS-K, O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate; CMH-OBN, chlorin e6-melanin-hyaluronic acid nanoparticles-oxidized bletilla striata polysaccharide microcapsules; Alb-PLP/NO NPs, albumin-coated poly(lactic-co-glycolic acid) (PLGA)-conjugated linear polyethylenimine diazeniumdiolate (LP/NO) nanoparticles; P@BDOX/β-lapachone-NO-NPs, peptides (pHLIPs)-poly(ethylene glycol) and nitrated gluconic acid copolymers @Doxorubicin prodrug/β-lapachone-NO; SPNAPt/NO, supramolecular prodrug nanoassemblies-platinum(IV) prodrug/NO; LPFe3O4 NPs, L-arginine-poly(acrylic acid)-hollow iron oxide nanoparticles; BPNs-Arg-GOx@MnO2, black phosphorus nanosheets-L-Arginine-glucose oxidase @MnO2 nanosheets; UC-ZIF/BER, upconversion nanoparticles-zeolitic nitro-/nitrile-imidazole framework-82-berbamine; HFLA-DOX, doxorubicin-heparin/folic acid/L-arginine; L-Arg@Ce6@P NPs, L-arginine@ chlorin e6@ poly-lactic-co-glycolic acid nanoparticle; HA@MOF/D-Arg, hyaluronic acid@ metal-organic frameworks/D-arginine; ArgCCN, poly-L-arginine modified carbon-dots-doped graphitic carbon nitride nanomaterial; RBCm/PAAVSNO/IR1061 + 1-MT NPs, red blood cell membrane/copolymer (poly(acrylamide-co-acrylonitrile-co-vinylimidazole)-S-nitrosothiols copolymer+1-methyl-tryptophan; NO-NCPs, NO-nanocapsules; Ptx@AlbSNO, paclitaxel@ NO donor-modified albumin; BSA-IRLA@RVs-RGD, BSA-L-Arginine-IR783@ red blood cells membrane derived vesicle-RGD; NO@HMs, NO-poly(lactic-co-glycolic acid) (PLGA) hollow microsphere; DPP-NF NPs, diketopyrrolopyrrole-4-nitro-3-trifluoromethylaniline nanoparticles; Lyso-Ru-NO@FA@C-TiO2, Lysosome-Ru-NO@ folic acid@ carbon-doped titanium dioxide nanoparticles; N-GQDs@Ru-NO@Gal, N-doped graphene quantum dots@ Ru-NO@ galactose derivative; CPNs, cocktail polyprodrug nanoparticles; L-Arg@PCN@Mem, L-arginine@ porous coordination network@ cancer cell membrane; P(IR/BNN6/AIPH)@Lip-RGD, IR 1061/BNN6/alkyl radical initiator@Liposome-RGD; Fe(II)-BNCP, 1,5-bis[(l-proline-1-yl)diazen-1-ium-1,2-diol-O2-yl]-2,4-dinitrobenzene nanoscale coordination polymer; ADAu@CuS YSNPs, l-arginine/Dox-loaded gold@ copper sulfide yolk–shell nanoparticls; IPO-NO, IR780-paclitaxel-NO donor-S-nitrosated human serum albumin; IMesNO/DOX@MCs, 1,3-bis-(2,4,6-trimethylphenyl)imidazolylidene nitric oxide/ Doxorubicin@ Micelles; PV-TS, polymeric nanovesicles- tetraphenylporphyrin- sodium nitroprusside; NO-M@DOX, Nitric Oxide Donor-containing polycarbonate-based micelles@ Doxorubicin; N-GQDs@Ru-Cl@TPP, N-doped graphene quantum dots@ ruthenium nitrosyl@ triphenylphosphonium; M@BPAG, macrophage membrane@ black phosphorus nanosheets-L-arginine-glucose oxidase; AI-MPHA NCs, indocyanine green/L-arginine-mesoporous core–shell structure nano-composites; PNOC-PDA/DOX, poly(L-cysteine)20-poly(ethylene oxide)45-SNO-polydopamine/ Doxorubicin; RBS-T-SCNPs, Roussin’s black salt- tocopheryl polyethylene glycol 1000 succinate-scintillating nanoparticles; HMs, hollow microsphere system; PEG-USMSs-SNO, PEG-upconversion nanotheranostic system- S-nitrosothiol; P-lapa-Fc, poly(ε-caprolactone) (PCL)-b-PArg-ferrocene; UMNOCC-PEG, copper peroxide nanodots-chlorin e6-polyethylene glycol-silicon pores; mCuMNO, S-nitrosoglutathione-copper-based metal-organic framework; T-NPCA/NO, cinnamaldehyde-NO nanoparticles.