Multistage nanoparticle delivery system for deep penetration into tumor tissue

Wong, Cliff; Stylianopoulos, Triantafyllos; Cui, Jian; Martin, John D.; Chauhan, Vikash P.; Jiang, Wen; Popović, Zoran V.; Jain, Rakesh K.; Bawendi, Moungi G.; Fukumura, Dai

doi:10.1073/pnas.1018382108

Cited by 949 publications

(831 citation statements)

References 38 publications

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“…To bolster nanomedicine tumor penetration and antitumor efficacy, two distinctive approaches have been investigated. One approach focuses on the design of sophisticated and smart nano‐drug delivery systems that are often difficult to scale up and translate 14. The other approach primes the tumor microenvironment (TME) to cater for the subsequent drug delivery 15.…”

Section: Introductionmentioning

confidence: 99%

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Zhu

Huang

et al. 2018

Advanced Science

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Hypoxia is a fundamental hallmark of solid tumors and helps contribute to chemotherapy resistance. Hyperbaric oxygen (HBO) therapy can overcome tumor hypoxia and promote chemotherapy antitumor efficacy; however, the simultaneous administration of some conventional chemotherapies, including doxorubicin (DOX), with HBO is considered an absolute contraindication. Here, DOX‐loaded liposome (Doxil) is coadministered with HBO to assess the safety and efficacy of this combination treatment. By overcoming tumor hypoxia, HBO not only improves Doxil tumor penetration by decreasing the collagen deposition but also sensitizes tumor cells to Doxil. As a result, the combination treatment synergistically inhibits H22 tumor growth, with a tumor inhibition rate of 91.5%. The combination of HBO with Doxil shows neither extra side effects nor promotion of tumor metastasis. These results collectively reveal that the combination of HBO with Doxil is an effective and safe treatment modality. As both HBO and Doxil are routinely used, their combination could quickly translate to clinical trials for patients with hypoxic solid tumors.

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Section: Introductionmentioning

confidence: 99%

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Zhu

Huang

et al. 2018

Advanced Science

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“…In addition, smaller particles (<10 nm), with better tumour diffusion capability [39], are readily eliminated from blood circulation and show inefficient EPR-based delivery [40,41]. The formulation described in this study has an appropriate size for increasing tumour accumulation through the EPR effect after administration via blood circulation.…”

Section: Cellular Uptake Of Nanoparticlesmentioning

confidence: 99%

Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

et al. 2016

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Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake. Incorporation of ICG in PGA nanoparticles provided the NIR-absorbing agent with time-dependent altered optical properties in the presence of cathepsin B. Having minimal dark toxicity, the formulation exhibited significant cytotoxicity upon NIR exposure. Combined use of the formulation with saporin, a ribosome-inactivating protein, resulted in synergistically enhanced cytotoxicity attributed to the photo-induced release of saporin from endo/lysosomes. The results suggest that this therapeutic approach can offer significant therapeutic benefit in the treatment of superficial malignancies, such as head and neck tumours.

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“…This way, delivery deep into the tumor tissue could be achieved [99]. Combining multiple tumor-targeting approaches can significantly increase the NP's selectivity towards the tumor.…”

Section: Targeting the Tumor Microenvironmentmentioning

confidence: 99%

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

et al. 2014

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Over the years research in the field of cancer immunotherapy has flourished, bringing about crucial breakthroughs, but at the same time revealing new and important pathways of immune suppression that put a break on the success of cancer immunotherapy. This review focuses on how nano-and micromaterials can be used to induce antitumor immune responses and what their role in overcoming immune suppression could be. It is now beyond question that this requires elegantly designed particles that can reach their target cells, deliver antigenic cargo and most importantly immune stimulants in order to provoke and sustain antitumor immunity.3

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Multistage nanoparticle delivery system for deep penetration into tumor tissue

Cited by 949 publications

References 38 publications

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Hyperbaric Oxygen Potentiates Doxil Antitumor Efficacy by Promoting Tumor Penetration and Sensitizing Cancer Cells

Cathepsin B-degradable, NIR-responsive nanoparticulate platform for target-specific cancer therapy

Nanoparticle design to induce tumor immunity and challenge the suppressive tumor microenvironment

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