Hypoxia-Responsive Mesoporous Nanoparticles for Doxorubicin Delivery

Abstract

Hypoxia, or low oxygen tension, is a common feature of solid tumors. Here, we report hypoxia-responsive mesoporous silica nanoparticles (HR-MSNs) with a 4-nitroimidazole-β-cyclodextrin (NI-CD) complex that is acting as the hypoxia-responsive gatekeeper. When these CD-HR-MSNs encountered a hypoxic environment, the nitroimidazole (NI) gatekeeper portion of CD-HR-MSNs disintegrated through bioreduction of the hydrophobic NI state to the hydrophilic NI state. Under hypoxic conditions, the release rate of doxorubicin (DOX) from DOX-loaded CD-HR-MSNs (DOX-CD-HR-MSNs) increased along with the disintegration of the gatekeeper. Conversely, DOX release was retarded under normoxic conditions. In vitro experiments confirmed that DOX-CD-HR-MSNs exhibit higher toxicity to hypoxic cells when compared to normoxic cells. Confocal microscopy images indicated that DOX-CD-HR-MSNs effectively release DOX into SCC-7 cells under hypoxic conditions. These results demonstrate that CD-HR-MSNs can release drugs in a hypoxia-responsive manner, and thus are promising drug carriers for hypoxia-targeted cancer therapy.

Ru(bpy)32+‐Loaded Mesoporous Silica Nanoparticles as Electrochemiluminescent Probes of a Lateral Flow Immunosensor for Highly Sensitive and Quantitative Detection of Troponin I

“…After Ru(bpy) 3 2+ loading, the zeta potential of the RMSNs shifted toward a more neutral state (−15.89 ± 0.67 mV), suggesting successful loading of Ru(bpy) 3 2+ into the MSN pores. [ 43,44 ] We then confirmed the successful loading of Ru(bpy) 3 2+ into the MSNs by absorbance spectra analysis. The spectrum of the RMSNs showed a maximum at 286 nm, whereas the carboxylated MSNs displayed a broad absorbance spectrum.…”

Tumor Microenvironment Sensitive Nanocarriers for Bioimaging and Therapeutics

“…Hypoxia also induces accelerated bioreductive reactions, and results in the upregulation of various bioreductive enzymes such as nitroreductase, quinone reductase, and azoreductase. [ 37 ] By exploiting this reductive microenvironment of tumor hypoxia, several hypoxia‐responsive nanocarriers have been developed using hypoxia‐sensitive moieties such as nitroaromatics, quinones, and azobenzene derivatives for improving therapeutic efficacy ( Table 2 ). [ 38 ] These hypoxia‐responsive chemical moieties have been carefully integrated in the amphiphilic block copolymeric nanocarriers or other nanosystems to induce structural transformation or selective scission of the responsive bonds (e.g., azobenzene bond), and thereby facilitating release of the active agents in the hypoxic TME.…”

Emerging Strategies in Anticancer Combination Therapy Employing Silica‐Based Nanosystems

“…In the first reported example on the topic, Park and co‐workers explored the possibility of a supramolecular assembly between nitroimidazole (NI) and βCD rings to act as nanogates. [ 58 ] In this model, the hypoxic conditions were able to reduce the NO 2 group to NH 2 , unable to bind the βCD caps, allowing DOX outflow from the mesopores. As a result, cellular assays against SCC‐7 cells under hypoxic conditions (0.1% O 2 , 5% CO 2 ) showed viability reductions up to 50%, in concordance with the limited effect of conventional chemotherapeutics on hypoxic cells.…”