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. 2018 Jan 1;8(2):533–548. doi: 10.7150/thno.21674

Table 2.

Promising solutions by nanoparticles to overcome barriers for cancer therapy.

Barrier for cancer therapy Promising solutions Example of used NPs Outcome Reference(s)
Irregular vessel permeability Activate the target by covalent conjugation of antibodies to NP surfaces. Immunoliposomes (Anti-HER2) Increased drug uptake and facilitated intracellular drug delivery. 69
Abnormal vessel porosity Prolong drug systemic circulation. Liposomes, polyethylene glycol (PEG) NPs. Improved drug availability and leading to superior tumor uptake. 70
Reduce vascular density and perfusion rates Reducing the interstitial fluid pressure in solid tumors. Combination of Taxane therapy with NPs or using a Hedgehog inhibitor (IPI-926) Improve the functional vascular density and enhance drug delivery to tumors. 71
Targeting and systemic treatment of cancer Delivered into the target tissue. Apolyelectrolyte complex (PEC) micelle-based siRNA delivery system. Efficiently delivered and readily taken up by cancer cells. 72
Hypoxic microenviornments Induce drug delivery. Hypoxia-sensitive polymeric micelles encapsulating DOX Effectively deliver the drugs into hypoxic cells. 73
Elevated interstitial fluid pressure Increasing interstitial transport of drug. Intermediate-sized nanoparticles (20-40 nm) targeting VEGFR-2 Decreases the interstitial fluid pressure and enhanced drug delivery. 74
Acidic microenviornments pH-sensitive NPs -Poly His containing nanogel and hydrogel NPs. -Gelatin nanoparticles Sped up drug release kinetics and increase drug efficacy. 75, 76
Multidrug-resistant (MDR) and drug-efflux pumps Stimuli-responsive drug release. Mesoporous silica nanoparticles (MSNs) Increase intracellular uptake and enhanced ability to overcome MDR. 77
Drug efflux and MDR phenotype Bypass the efflux pumps through endocytosis. Cycloporin A (CyA) and doxorubicin in polyalkylcyanoacrylate NPs. Prevent complex side effects and regularly deliver NPs to the target cells. 78
Reduce the apoptotic threshold in MDR Increase the apoptotic activity Combination therapy of tamoxifen and paciltaxel nanoparticles. Significant enhancement in antitumor efficacy without any toxicity. 79
Poor oral availability, short half-life and continuous parenteral administration Increase intestinal absorption and drug selectivity Nanopolymeric Lodamin (TNP-470 conjugated to mono-methoxy-polyethylene glycol-polylactic acid) Selectively inhibited tumor growth and metastasis without any side effect. 8