Targeting the Tumor Core: Hypoxia-Responsive Nanoparticles for the Delivery of Chemotherapy to Pancreatic Tumors

Confeld, Matthew; Mamnoon, Babak; Li, Feng; Jensen-Smith, Heather; Ray, Priyanka; Froberg, James; Kim, Jiha; Hollingsworth, Michael A.; Quadir, Mohiuddin; Choi, Yongki; Mallik, Sanku

doi:10.1021/acs.molpharmaceut.0c00247

Cited by 52 publications

(57 citation statements)

References 90 publications

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“…To rule out the possibility that attenuated cellular response to the drug in hypoxia is due to less efficient drug delivery into the cells, we investigated the amount of drug uptake Oncotarget 5 www.oncotarget.com by cells in normoxia and hypoxia (Figure 4). Intrinsically fluorescent doxorubicin [45,46] and gemcitabine loaded into lissamine rhodamine nanocarriers were used for the detection of drugs using fluorescence microscopy (see "Materials and Methods" for more details) [47,48]. After 3 hours of drug treatment, nuclear localization of drugs was observed.…”

Section: Resultsmentioning

confidence: 99%

“…The MDA-MB-231 cells were then treated with 5 μM doxorubicin for 3 hours. Gemcitabine was loaded into nanocarriers composed of biocompatible and biodegradable polylactic acid (PLA) and polyethylene glycol (PEG) polymers, along with fluorescent lissamine-rhodamine dye, as previously described [ 47 , 48 ]. Briefly, the PLA-PEG polymer and lissamine-rhodamine dye were mixed at a 95:5 molar ratio with 0.2 mg/ml gemcitabine solution.…”

Section: Methodsmentioning

confidence: 99%

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Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy

et al. 2021

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The changes in cellular structure play an important role in cancer cell development, progression, and metastasis.By exploiting single-cell, force spectroscopy methods, we probed biophysical and biomechanical kinetics (stiffness, morphology, roughness, adhesion) of brain, breast, prostate, and pancreatic cancer cells with standard chemotherapeutic drugs in normoxia and hypoxia over 12-24 hours. After exposure to the drugs, we found that brain, breast, and pancreatic cancer cells became approximately 55-75% less stiff, while prostate cancer cells became more stiff, due to either drug-induced disruption or reinforcement of cytoskeletal structure. However, the rate of the stiffness change decreased up to 2-folds in hypoxia, suggesting a correlation between cellular stiffness and drug resistance of cancer cells in hypoxic tumor microenvironment. Also, we observed significant changes in the cell body height, surface roughness, and cytoadhesion of cancer cells after exposure to drugs, which followed the trend of stiffness. Our results show that a degree of chemotherapeutic drug effects on biomechanical and biophysical properties of cancer cells is distinguishable in normoxia and hypoxia, which are correlated with alteration of cytoskeletal structure and integrity during drug-induced apoptotic process.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy

et al. 2021

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“…Compared with the untreated control group, the polymersomes reduced tumor growth by nearly 250% in mice, and significantly increased necrosis by 60% within the tumors. [ 120 ] Moreover, He et al. designed a cell‐penetrating peptide‐camptothecin prodrug (Apt/CPP‐CPTD NPs), wherein an ECM component (tenascin‐C) targeting GBI‐10 aptamer was modified onto CPP for in vivo PDAC‐homing.…”

Section: Pdac‐tailored Nanomaterials For Therapeutic Strategiesmentioning

confidence: 99%

Tailor‐Made Nanomaterials for Diagnosis and Therapy of Pancreatic Ductal Adenocarcinoma

Xia

Lee

et al. 2021

Advanced Science

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Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide due to its aggressiveness and the challenge to early diagnosis and treatment. In recent decades, nanomaterials have received increasing attention for diagnosis and therapy of PDAC. However, these designs are mainly focused on the macroscopic tumor therapeutic effect, while the crucial nano–bio interactions in the heterogeneous microenvironment of PDAC remain poorly understood. As a result, the majority of potent nanomedicines show limited performance in ameliorating PDAC in clinical translation. Therefore, exploiting the unique nature of the PDAC by detecting potential biomarkers together with a deep understanding of nano–bio interactions that occur in the tumor microenvironment is pivotal to the design of PDAC‐tailored effective nanomedicine. This review will introduce tailor‐made nanomaterials‐enabled laboratory tests and advanced noninvasive imaging technologies for early and accurate diagnosis of PDAC. Moreover, the fabrication of a myriad of tailor‐made nanomaterials for various PDAC therapeutic modalities will be reviewed. Furthermore, much preferred theranostic multifunctional nanomaterials for imaging‐guided therapies of PDAC will be elaborated. Lastly, the prospects of these nanomaterials in terms of clinical translation and potential breakthroughs will be briefly discussed.

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“…1, 4), 24 antibacterial, anti-infectives, antprotozoal, antituberculosis, antitrypanosomiasis compounds 5,18,19,[25][26][27][28][29][30][31][32] . The phenanthridine ring systems are also used in lockable colorimetric fluorescence molecular switch, PET tracers, and in material science applications 4,15,22,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] .…”

Section: Introductionmentioning

confidence: 99%

Domino Suzuki-Miyaura Cross-Coupling and Oxidative Condensation Reaction: An Approach Towards Synthesis of Phenanthridine and Its Analogues

Nuree¹,

2021

Preprint

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Phenanthridines belong to a very important class of nitrogen containing heterocylic compounds and constitute core structure of many natural alkaloids such as trisphaeridine and nitidine. Quarternarybenzo[c]phenanthridine alkaloids (QBA) represented by sanguinarine(SA), chelerythrine (CHE), and fagaronine (FA) exhibit antifungal and nematocidal properties and also serve as the core structure of broad range of medicinally active molecules showing anti-tumor activity, anti-viral property, anti-neoplastic or mutagenic activity through DNA-intercalation. Phenanthridines are also utilized for the synthesis of compounds of therapeutic interests such as anticancer platinum complex typified by phenanthriplatin antibacterial, anti-infectives, antprotozoal, antituberculosis, antitrypanosomiasis compounds. Although conventional synthetic methods towards their development showed their own advantages, they generally involved either multistep processes with low yield, or starting materials which are not readily available or requirement of prefunctionalization. Hence herein we present the development of an efficient and convenient synthetic methodology towards these versatile compounds. <br>

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Targeting the Tumor Core: Hypoxia-Responsive Nanoparticles for the Delivery of Chemotherapy to Pancreatic Tumors

Cited by 52 publications

References 90 publications

Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy

Dynamic cellular biomechanics in responses to chemotherapeutic drug in hypoxia probed by atomic force spectroscopy

Tailor‐Made Nanomaterials for Diagnosis and Therapy of Pancreatic Ductal Adenocarcinoma

Domino Suzuki-Miyaura Cross-Coupling and Oxidative Condensation Reaction: An Approach Towards Synthesis of Phenanthridine and Its Analogues

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