Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy

Abstract

Background Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. Results The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment. Conclusions By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited. Graphic abstract

Metal-based nano-delivery platform for treating bone disease and regeneration

“…Using this method, non-porous nanomaterials can be combined with therapeutic molecules via electrostatic attraction, non-covalent hydrophobic interactions, π–π stacking, and hydrogen bonding. Benefiting from tunable pore, high specific surface areas, and active surfaces, some porous NPs can also be loaded using drugs via this method ( Chen et al, 2021 ). Therefore, postsynthetic encapsulation/loading is a suitable method for most MNPs; however, the difference is that for MNPs with pores, small drug molecules can be encapsulated inside the MNPs through the pore size; for MNPs without sufficient pore sizes or if the pores are already occupied, drug molecules can only be loaded onto the nanomaterial surface or functionalized modified surfaces.…”

The emerging role of cancer nanotechnology in the panorama of sarcoma

“…Starting from this, a number of sarcoma passively targeted DDS have been studied. An example is the study of Chen and colleagues who developed an mPEG-PLA-based nanosystem ( Chen et al, 2021 ) loaded with docetaxel assessing their passive targeting and activity in mice bearing S180 sarcoma tumor. Sasatsu et al (2008) synthesized a methoxypolyethylene glycol amine-poly (DL-lactic acid) copolymer nanoparticles loaded with pyrene-ended poly (DL-lactic acid) providing evidence of passive sarcoma-180 tumor targeting.…”

Tumor microenvironment penetrating chitosan nanoparticles for elimination of cancer relapse and minimal residual disease

“…There are three general anticancer strategies based on tumor hypoxia: (i) harnessing it for the development of bioresponsive (hypoxia-responsive) nanomedicines; (ii) alleviating the hypoxia using vascular normalization agents (antiangiogenic therapy) or increasing oxygen level externally [oxygen delivery using hemoglobin ( 98 ) or perfluorocarbon] or internally [using oxygen generators called enzymes, which employ MnO 2 ( 99 ) and catalase (CAT) ( 100 ) to generate O 2 from H 2 O 2 present abundantly in TME]; and, finally, (iii) oxygen depletion or starvation therapy, which aims to kill tumor cells by exacerbation of hypoxia and oxygen/nutrient depletion, as practiced by vascular infarction/disruption therapy using vascular disrupting agents or delivery of thrombosis-inducing agents such as coagulase fusion proteins ( 101 , 102 ) or thrombin delivery ( 103 ) using a nanorobot to the tumor site to induce thrombosis selectively in tumor blood vessels. Oxygen depletion itself can be achieved externally by PDT and radiotherapy, which consumes intratumoral O 2 to generate ROS or endogenously by inherent oxygen-consuming materials such as magnesium silicide (Mg 2 Si) ( 104 ), perfluorotributylamine (PFTBA) ( 105 ), or glucose oxidase (GO X ) ( 106 ). Mostly, for a better efficacy, the combination of these approaches together ( 107 ) or with other approaches such as chemotherapy ( 99 ), radiotherapy, SDT ( 100 ), immunotherapy, and PDT ( 108 ) is desired.…”