Magnetically Actuated Active Deep Tumor Penetration of Deformable Large Nanocarriers for Enhanced Cancer Therapy

Abstract

The intrinsic pathological microenvironment of tumor tissue enforces barriers to the passive diffusion of nanomedicine, which results in inefficient tumor penetration of drugs and unsatisfactory therapeutic efficacy. Various strategies have been developed to improve the tumor penetration of nanomedicine, but they mostly overcome the barriers separately at different steps in a passive diffusion process. Here, the development of a large polymeric nanocarrier, DA T-PPE D&F (≈180 nm), is reported, which comprises a flowable polyphosphoester core, ferrimagnetic nanocubes, and a tumor extracellular pH-sensitive transactivator of transcription (TAT). Compared with a polylactic acid-based nanocarrier with a rigid core, this deformable DA T-PPE D&F with a similar diameter exhibits efficient penetration into the deep tumor tissue under magnetic actuation and an enhanced reactivation rate of the pH esensitive TAT. Therefore, DA T-PPE D&F is able to efficiently deliver doxorubicin into most tumor cells in vivo, and the superior anticancer effect indicates the potential of DA T-PPE D&F as a universal, responsive, and active nanocarrier to deliver various hydrophobic drugs into the deep tumor tissue.

Rational design of ROS-responsive nanocarriers for targeted X-ray-induced photodynamic therapy and cascaded chemotherapy of intracranial glioblastoma

“…Among the various strategies for nanocarriers to cross the BBB, utilizing specific receptors that are expressed at the BBB for active targeting is the most commonly preferred method due to its noninvasive and feasible characteristics. [11][12][13] In recent years, pioneering studies have confirmed that the lowdensity lipoprotein receptor-related protein-1 (LRP-1) is overexpressed not only at the BBB but also at the cytoplasm and surface of the GBM cells. 14 Due to its dual targeting mechanism and higher efficiency than lactoferrin, transferrin and avidin, angiopep-2 (Ang, a targeted peptide for LRP-1) has emerged as a more ideal candidate for nanocarrier modification to facilitate their BBB penetration and subsequent internalization by brain parenchymal cells.…”

Tumor acidity/redox hierarchical-activable nanoparticles for precise combination of X-ray-induced photodynamic therapy and hypoxia-activated chemotherapy

“…These results are in good agreement with previous findings, demonstrating that tumor pH substantially enhances the internalized DA TAT-NP VT content by recovering its TAT ligand function. 56,57…”

“…These results are in good agreement with previous findings, demonstrating that tumor pH substantially enhances the internalized DA TAT-NP VT content by recovering its TAT ligand function. 56,57 3.3 Cell killing of DA TAT-NP VT in vitro According to our design, the increased intracellular VP content could improve the efficiency of X-PDT treatment under external X-ray exposure. Subsequently, the hypoxic condition induced by radiotherapy and PDT would activate TPZ to release cytotoxic oxidizing radicals for efficient chemotherapy.…”

Amorphous ferric oxide-coating selenium core–shell nanoparticles: a self-preservation Pt(iv) platform for multi-modal cancer therapies through hydrogen peroxide depletion-mediated anti-angiogenesis, apoptosis and ferroptosis

“…1i), confirming that USIO was typically ferromagnetic, consistent with the previous report. 33 However, unlike the Scheme 1 Schematic illustration of the preparation of iAIO@NSe-Pt and the synergistic actions of anti-angiogenesis, chemo-, and chemodynamic therapy induced by iAIO@NSe-Pt.…”