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 |