Lipase‐Triggered Water‐Responsive “Pandora's Box” for Cancer Therapy: Toward Induced Neighboring Effect and Enhanced Drug Penetration

Abstract

Insufficient drug release as well as poor drug penetration are major obstacles for effective nanoparticles (NPs)-based cancer therapy. Herein, the high aqueous instability of amorphous calcium carbonate (ACC) is employed to construct doxorubicin (DOX) preloaded and monostearin (MS) coated "Pandora's box" (MS/ACC-DOX) NPs for lipase-triggered water-responsive drug release in lipase-overexpressed tumor tissue to induce a neighboring effect and enhance drug penetration. MS as a solid lipid can prevent potential drug leakage of ACC-DOX NPs during the circulatory process, while it can be readily be disintegrated in lipase-overexpressed SKOV3 cells to expose the ACC-DOX core. The high aqueous instability of ACC will lead to burst release of the encapsulated DOX to induce apoptosis and cytotoxicity to kill the tumor cells. The liberated NPs from the dead or dying cells continue to respond to the ubiquitous aqueous environment to sufficiently release DOX once unpacked, like the "Pandora's box", leading to severe cytotoxicity to neighboring cells (neighboring effect). Moreover, the continuously released free DOX molecules can readily diffused through the tumor extracellular matrix to enhance drug penetration to deep tumor tissue. Both effects contribute to achieve elevated antitumor benefits.

Water‐Responsive Hybrid Nanoparticles Codelivering ICG and DOX Effectively Treat Breast Cancer via Hyperthermia‐aided DOX Functionality and Drug Penetration

“…We recently explored nanosized amorphous calcium carbonate (ACC), which can be more readily obtained by various simple methods, unlike crystallized calcium carbonate (CCC) that is usually in the micrometer range of size. The high aqueous instability of ACC, which is responsible for its quick drug release in aqueous medium, has generally been recognized as the major obstacle for employing ACC as a DDSs.…”

Cancer cell membrane coated silica nanoparticles loaded with ICG for tumour specific photothermal therapy of osteosarcoma

“…Drug delivery systems (DDS) based on nanoparticles have been demonstrated to exert enhanced bioavailability while at the same time can greatly reduce undesired side effects as compared to free drugs, which has been well recognized as a promising alternative for effective cancer therapy [1][2][3]. Therefore, different kinds of DDSs based on various materials (varying from organic to inorganic ones) have been explored [1,[4][5][6]. Silica nanoparticles (SLN) as one of the most widely adopted material is emerging as a promising candidate due to its versatile merits [7][8][9].…”

Heparin coated meta-organic framework co-delivering doxorubicin and quercetin for effective chemotherapy of lung carcinoma

“…The competitive uptake assay strongly suggested that the surface-anchored HA was involved in the variations of cellular uptake between different formulations, which suggested that HA modification might be able to guide the DDS to the CD44 receptor overexpressed cells with high affinity for the same molecule. 30 The in vivo targeting assay in the current study clearly demonstrated that the tumour targeting nature of HA could guide the HM to accumulate in the in vivo tumour tissue. 31,32 Moreover, the in vivo antitumour assay further confirmed the enhanced anticancer benefits of Dox and Que in the current study.…”