Advanced nanotechnology for hypoxia-associated antitumor therapy

Abstract

Two major strategies of using and overcoming hypoxia in advanced nanotechnology.

A Ru(II)‐Based Nanoassembly Exhibiting Theranostic PACT Activity in NIR Region

“…As shown in Figure S13 in the Supporting Information, the photoinactivation abilities of Ru‐PEG and Ru‐PEG‐BP against A549 cells had only a slight decrease in the hypoxic condition with respect to that in a normoxic condition. Considering the fact that many solid tumors are in a hypoxic microenvironment, [ 13 ] the PACT agents may find wide applications in clinic.…”

The targetable nanoparticle BAF312@cRGD-CaP-NP represses tumor growth and angiogenesis by downregulating the S1PR1/P-STAT3/VEGFA axis in triple-negative breast cancer

“…BAF312 is a fat-soluble drug; therefore, we encapsulated BAF312 into pH-sensitive and tumor-targeted nanoparticles to form the BAF312@cRGD-CaP-NPs, of which constructed with a PEG2000 hydrophilic chain modified with cRGD, a DSPE hydrophobic chain and a degradable calcium-phosphate shell. The features of the shell-core structure NPs, including the proper size, the αvβ3 and αvβ5 integrin receptor cRGD and negative charge, ensure their effective penetration of discontinuous tumor blood vessels via EPR effects and active targeting to tumor sites mediated by cRGD and long-term circulation [ 37 , 38 , 43 ]. In addition, the calcium-phosphorus system is sensitive to pH changes, which ensures that the particles become positively charged in the acidic tumor microenvironment [ 42 ] and increases the absorption of NPs by tumor cells and vascular cells [ 44 ].…”

“…The formed nanoparticles were used as the BAF312 delivery system (BAF312@cRGD-CaP-NPs). The outstanding features of the generated NPs were as follows: (1) The nanoparticles have a diameter of 109.9 ± 1.002 nm, which can utilize the enhanced permeability and retention effect (EPR) to accumulate in the tumor site [ 37 ]; (2) cRGD has specific affinity for the αvβ3 and αvβ5 integrins, which are highly expressed on the breast cancer cells and endothelial cells of tumor angiogenic vessels [ 38 , 39 ]; (3) DSPE is a phospholipid and is harmless to the human body, and PEG2000 is approved by the FDA for usage in the human body [ 40 ], which enables the nanoparticle to have long-lasting properties in the blood circulation [ 41 ]; the calcium-phosphorus system is sensitive to pH changes, thereby ensuring the accurate drug release of nanoparticles in the acidic tumor microenvironment [ 42 ]; (4) The negative charge of − 10.6 ± 0.056 mV of the nanoparticles assists them in evading clearance by immune cells and enables them to have long-lasting circulation; the particles become positively charged at + 6.80 ± 0.013 mV in the acidic tumor niche, ensuring that they are efficiently taken up by tumor cells, as tumors are apt to adsorb positively charged nanoparticles [ 43 , 44 ]; and (5) In addition, calcium and phosphorus are essential elements for human, while breast cancer patients are prone to calcium deficiency due to hormone abnormalities [ 45 ]; thus, calcium and phosphorus can be the supplements for patients with BRCA or TNBC. Above all, pH-sensitive and tumor-targeted nanoparticle is a competent drug delivery system for BAF312 to treat breast cancer.…”

An Alternating Irradiation Strategy‐Driven Combination Therapy of PDT and RNAi for Highly Efficient Inhibition of Tumor Growth and Metastasis

“…[1,6] However, several unresolved challenges restrict its wide application in the clinic, including hypoxia, which induces the overexpression of a series of oxygen-regulated genes and is one of the most important factors that not seriously affects the treatment efficacy of PDT but plays a crucial role in tumor recurrence and metastasis. [7][8][9][10] Because of the imperfect vascular system, tumors are usually exposed to low levels of oxygen. Following serve vascular damage caused by PDT, the blood supply will be cut off, which will further worsen the anoxic environment and seriously affect the treatment results, [11][12][13] especially in deep-seated tumors.…”

“…[ 1,6 ] However, several unresolved challenges restrict its wide application in the clinic, including hypoxia, which induces the overexpression of a series of oxygen‐regulated genes and is one of the most important factors that not seriously affects the treatment efficacy of PDT but plays a crucial role in tumor recurrence and metastasis. [ 7–10 ]…”