Small Morph Nanoparticles for Deep Tumor Penetration via Caveolae-Mediated Transcytosis

Zhang, Zipeng; Wang, Tianqi; Yang, Rui; Fu, Shunli; Guan, Li; Hou, Teng; Mu, Weiwei; Pang, Xiuping; Liang, Shuang; Liu, Yongjun; Zhang, Na

doi:10.1021/acsami.0c06872

Cited by 31 publications

(26 citation statements)

References 56 publications

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“…Besides enhanced tumor accumulation, potent drug delivery also relies on deep tumor penetration. , B16F10 tumor spheroids were employed as a three-dimensional (3D) model to mimic the tumor tissues in vitro to preliminarily evaluate the penetration capability of PPN. Tumor spheroids were visualized using a CLSM with Z -stack scanning after treatment with Cou 6-loaded PPN with/without laser irradiation.…”

Section: Results and Discussionmentioning

confidence: 99%

Multifunctional Size-Expandable Nanomedicines Enhance Tumor Accumulation and Penetration for Synergistic Chemo-Photothermal Therapy

Yang

et al. 2021

ACS Appl. Mater. Interfaces

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Size expansion can effectively improve tumor accumulation of nanocarriers where precise control is required. A dual-responsive nanocarrier stimulated by both endogenous pH and exogenous heat stimuli can change its size. Herein, a nanoparticle composed of poly(N,N-diethyl acrylamide) (PDEAA) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) is developed. The antitumor drug celastrol (CLT) and the photosensitizer indocyanine green (ICG) are then loaded in it to form CIPP. ICG generates heat under near-infrared (NIR) stimulation to kill tumor cells and enhance CIPP penetration. Meanwhile, CIPP expands in response to hyperthermia and acid tumor microenvironments, preventing itself from returning to the blood flow, thus accumulating in tumor sites. Ultimately, the acidic lysosomal environment in tumor cells disintegrates CIPP to release CLT, directly inducing immunogenic cell death and sensitizing tumor cells for hyperthermia by disrupting the interaction of heat shock protein 90 and P50cdc37. Most of the tumors in B16F10-bearing mice are eradicated after single laser irradiation. The dual-responsive CIPP with multiple functions and simple design displays a synergistic antitumor effect. This study provides a basis for developing size-expandable stimulus-responsive drug delivery systems against tumors.

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Section: Results and Discussionmentioning

confidence: 99%

Multifunctional Size-Expandable Nanomedicines Enhance Tumor Accumulation and Penetration for Synergistic Chemo-Photothermal Therapy

Yang

et al. 2021

ACS Appl. Mater. Interfaces

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“…Mitochondrial-targeting drug carriers should not only shield the positive charge of CTPP but should also successfully escape from the trapping of endosomes/secondary lysosomes. Recent reports have revealed that the positively charged nanoparticles could be rapidly internalized via caveolae-mediated endocytosis and then by vesicle-mediated transcytosis [ 34 , 35 ]. This transcytosis process might explain why CTPP-containing nanoparticles have low mitochondrial-targeting efficiency.…”

Section: Discussionmentioning

confidence: 99%

Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery

Shueng

Hou

et al. 2022

IJMS

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Mitochondrial-targeting therapy is considered an important strategy for cancer treatment. (3-Carboxypropyl) triphenyl phosphonium (CTPP) is one of the candidate molecules that can drive drugs or nanomedicines to target mitochondria via electrostatic interactions. However, the mitochondrial-targeting effectiveness of CTPP is low. Therefore, pH-sensitive polymer–liposome complexes with charge-conversion copolymers and CTPP-containing cationic liposomes were designed for efficiently delivering an anti-cancer agent, ceramide, into cancer cellular mitochondria. The charge-conversion copolymers, methoxypoly(ethylene glycol)-block-poly(methacrylic acid-g-histidine), were anionic and helped in absorbing and shielding the positive charges of cationic liposomes at pH 7.4. In contrast, charge-conversion copolymers became neutral in order to depart from cationic liposomes and induced endosomal escape for releasing cationic liposomes into cytosol at acidic endosomes. The experimental results reveal that these pH-sensitive polymer–liposome complexes could rapidly escape from MCF-7 cell endosomes and target MCF-7 mitochondria within 3 h, thereby leading to the generation of reactive oxygen species and cell apoptosis. These findings provide a promising solution for cationic liposomes in cancer mitochondrial-targeting drug delivery.

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“…3D tumor spheroids of B16 cells were prepared by hanging drop method according to literature reports. [ 32 ] In brief, 20 µL of the 0.24% methylcellulose culture medium solution containing 3000 cells were transferred onto the lid of 24‐well culture plates and were inverted over culture plate. These cells were incubated for one week.…”

Section: Methodsmentioning

confidence: 99%

An Integrated Nanoaircraft Carrier Modulating Antitumor Immunity to Enhance Immune Checkpoint Blockade Therapy

Liang

Liu

Gao

et al. 2021

Adv Funct Materials

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Immune checkpoint blockade (ICB) therapy revolutionizes cancer therapeutics. However, the effectiveness of ICB therapy is restricted. Focusing on the tumor itself and the immune system, an integrated nanoaircraft carrier that coloaded three therapeutic agents (NNG/OTC) to eradicate tumor cells, enhance T-cells intratumoral infiltration, and relieve the inhibition of tumor immunosuppressive microenvironment (TIM) is designed. First, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is used to combine with oxaliplatin for reducing tumor burden. Second, oxaliplatin is used to elicit immunogenic cell death and combine with cytosine-phosphate-guanine (CpG) to promote dendritic cells maturation, ultimately increasing T-cells intratumoral infiltration. Third, CpG is further used to repolarize M2 type of tumorassociated macrophages, thus reversing immunosuppression of TIM. The nanoaircraft carrier can effectively arrive at the tumor site and detach smallsized nanoparticles under a high concentration of matrix metalloproteinase-2, which promotes deep tumor penetration. Under the mediation of targeting ligands, three therapeutic agents loaded in small-sized nanoparticles could be launched to their target cells. NNG/OTC modulates the antitumor immunity and exhibits excellent tumor inhibition when in combination with ICB therapy, indicating the increased response of ICB therapy. Collectively, NNG/OTC can co-deliver various drugs with different physicochemical properties and provide a promising strategy for enhancing ICB therapy.

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Small Morph Nanoparticles for Deep Tumor Penetration via Caveolae-Mediated Transcytosis

Cited by 31 publications

References 56 publications

Multifunctional Size-Expandable Nanomedicines Enhance Tumor Accumulation and Penetration for Synergistic Chemo-Photothermal Therapy

Multifunctional Size-Expandable Nanomedicines Enhance Tumor Accumulation and Penetration for Synergistic Chemo-Photothermal Therapy

Charge Conversion Polymer–Liposome Complexes to Overcome the Limitations of Cationic Liposomes in Mitochondrial-Targeting Drug Delivery

An Integrated Nanoaircraft Carrier Modulating Antitumor Immunity to Enhance Immune Checkpoint Blockade Therapy

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