Redox-activatable hyaluronic acid-SS-mertansine prodrug: superior drug loading, enhanced toleration, and targeted breast tumor therapy

Characterization of targeted redox-sensitive micelles self-assembled from polymer–drug conjugates exhibiting conspicuous drug loading capabilities, selective cellular uptake, rapid intracellular disassembly and drug release is presented.

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Novel CD44-targeting and pH/redox-dual-stimuli-responsive core–shell nanoparticles loading triptolide combats breast cancer growth and lung metastasis

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00934-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jinfeng Shi ◽

Yali Ren ◽

Jiaqi Ma ◽

Xi Luo ◽

Jiaxin Li ◽

...

Keyword(s):

Breast Cancer ◽

Hyaluronic Acid ◽

Drug Release ◽

Lung Metastasis ◽

Drug Loading ◽

Tumor Therapy ◽

Systemic Toxicity ◽

Migration And Invasion ◽

Stimuli Responsive ◽

Cd44 Targeting

Abstract Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

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Non-Invasive Monitoring of Breast Tumor Oxygenation: A Key to Tumor Therapy Planning and Tumor Prognosis

10.21236/ada399998 ◽

2001 ◽

Author(s):

Hanli Liu

Keyword(s):

Breast Tumor ◽

Tumor Therapy ◽

Tumor Oxygenation ◽

Invasive Monitoring ◽

Therapy Planning ◽

Non Invasive ◽

Tumor Prognosis

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Non-Invasive Monitoring of Breast Tumor Oxygenation: A Key to Tumor Therapy Planning and Tumor Prognosis

10.21236/ada413009 ◽

2002 ◽

Author(s):

Hanli Liu

Keyword(s):

Breast Tumor ◽

Tumor Therapy ◽

Tumor Oxygenation ◽

Invasive Monitoring ◽

Therapy Planning ◽

Non Invasive ◽

Tumor Prognosis

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Hyaluronan based Multifunctional Nano-carriers for Combination Cancer Therapy

Current Topics in Medicinal Chemistry ◽

10.2174/1568026620666200922113846 ◽

2020 ◽

Vol 20 ◽

Author(s):

Menghan Gao ◽

Hong Deng ◽

Weiqi Zhang

Keyword(s):

Cancer Therapy ◽

Combination Therapy ◽

Cancer Cells ◽

Drug Loading ◽

Tumor Therapy ◽

Drug Carriers ◽

Functional Sites ◽

Therapeutic Modalities ◽

Combination Cancer Therapy ◽

Targeting Strategy

: Hyaluronan (HA) is a natural linear polysaccharide that has excellent hydrophilicity, biocompatibility, biodegradability, and low immunogenicity, making it one of the most attractive biopolymers used for biomedical researches and applications. Due to the multiple functional sites on HA and its intrinsic affinity for CD44, a receptor highly expressed on various cancer cells, HA has been widely engineered to construct different drug-loading nanoparticles (NPs) for CD44- targeted anti-tumor therapy. When a cocktail of drugs is co-loaded in HA NP, a multifunctional nano-carriers could be obtained, which features as a highly effective and self-targeting strategy to combat the cancers with CD44 overexpression. The HA-based multidrug nano-carriers can be a combination of different drugs, various therapeutic modalities, or the integration of therapy and diagnostics (theranostics). Up to now, there are many types of HA-based multidrug nano-carriers constructed by different formulation strategies including drug co-conjugates, micelles, nano-gels and hybrid NP of HA and so on. This multidrug nano-carrier takes the full advantages of HA as NP matrix, drug carriers and targeting ligand, representing a simplified and biocompatible platform to realize the targeted and synergistic combination therapy against the cancers. In this review, recent progresses about HA-based multidrug nano-carriers for combination cancer therapy are summarized and its potential challenges for translational applications have been discussed.

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Preclinical investigations revealed possibilities for Salmonella tumor treatment. Bacteria can also be coupled to nanomaterials enabling drug-loading, photocatalytic and/or magnetic properties, using the bacteria's net negative charge

10.31219/osf.io/embqk ◽

2021 ◽

Author(s):

Moataz Dowaidar

Keyword(s):

Clinical Trials ◽

Cancer Therapy ◽

Cancer Treatment ◽

Negative Charge ◽

Human Cancer ◽

Drug Loading ◽

Tumor Therapy ◽

Preclinical Research ◽

Immunodeficient Mice ◽

Virulence Attenuation

Except in human clinical trials, preclinical tests showed the potential of Salmonella bacteria for tumor therapy. There are still various challenges to tackle before salmonella bacteria may be employed to treat human cancer. Due to its pathogenic nature, attenuation is essential to minimize the host's harmful effects of bacterial infection. Loss of anticancer efficacy from bacterial virulence attenuation can be compensated by giving therapeutic payloads to microorganisms. Bacteria can also be linked to micro-or nanomaterials with diverse properties, such as drug-loaded, photocatalytic and/or magnetic-sensing nanoparticles, using the net negative charge of the bacteria. Combining bacteria-mediated cancer treatment with other medicines that have been clinically shown to be helpful but have limits may provide surprising therapeutic results. Recently, this strategy has received attention and is underway. The use of live germs for cancer treatment has not yet been approved for human clinical trials. The non-invasive oral form of administration benefits from safety, making it more suitable for clinical cancer patients.Infection of live germs through systemic means, on the other hand, involves toxicity risk. Although Salmonella bacteria can be genetically manipulated with high tumor targeting, harm to normal tissues can not be excluded when medications with nonspecific toxicity are administered. It is preferred if the action of selected drugs may be restricted to the tumor site rather than healthy tissues, thereby boosting cancer therapy safety. In recent years, many regulatory mechanisms have been developed to manage pharmaceutical distribution through live bacterial vectors. Engineered salmonella can accumulate 1000 times greater than normal tissue density in the tumor. The QS-regulated mechanism, which initiates gene expression when bacterial density exceeds a particular threshold level, also promises Salmonella bacteria for targeted medication delivery. Nanovesicle structures of Salmonella bacteria can also be used as biocompatible nanocarriers to deliver functional medicinal chemicals in cancer therapy. Surface-modified nanovesicles preferably attach to tumor cells and are swallowed by receptor-mediated endocytosis before being destroyed to release packed drugs. The xenograft methodology, which comprises the implantation of cultivated tumor cell lines into immunodeficient mice, has often been used in preclinical research revealing favorable results about the anticancer effects of genetically engineered salmonella.

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A Low Dose of Hydrous Icaritin Nano-Formulation with Remarkable Efficacy and Tumor Targeting in Cancer Therapy

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3176 ◽

2021 ◽

Vol 17 (10) ◽

pp. 2003-2013

Author(s):

Jingxin Fu ◽

Yian Wang ◽

Haowen Li ◽

Likang Lu ◽

Hui Ao ◽

...

Keyword(s):

Cancer Therapy ◽

Tumor Targeting ◽

Low Dose ◽

Drug Loading ◽

Tumor Therapy ◽

High Dose ◽

Inhibition Rate ◽

Tumor Inhibition ◽

Nano Formulation ◽

Tumor Inhibition Rate

Background: The use of chemotherapeutic drugs is restricted in the tumor-therapy because of the severely toxic and side effects among most important factors. The active herbal extracts are always used as a high dose while in the tumortherapy to achieve good anti-tumor effects. Hydrous icaritin has a high activity while there are few existing dosage forms as a result of low solubility in water and poor bioavailability. Results: The prepared hydrous icaritin nanorods (DP-HICT NRs) using mPEG2000-DSPE as a stabilizer, presented a narrow distribution of particle size with of 217 nm and a properly high drug-loading content of approximately 65.3±1.5%. A low dose of hydrous icaritin nano-formulation shows remarkable efficacy in cancer therapy (tumor inhibition rate: 61.36±10.80%) compared with the same dose of Paclitaxel injection (tumor inhibition rate: 66.80±4.43%), which approved as medicaments. Not only that, DP-HICT NRs can escape the clearance of the immune system and enhance targeting ability to the tumor site with only one excipient and such a low dose. Conclusions: This kind of nanoparticles contain a low dose of HICT used mPEG2000-DSPE as a stabilizer, while can achieve good tumor targeting as some active targeting agents and an anti-tumor effect as the PTX injection. There are broad prospects in drug safety, anti-tumor efficacy and even prognosis.

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Near-infrared light triggered liposomes combining photodynamic and chemotherapy for synergistic breast tumor therapy

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2018.10.019 ◽

2019 ◽

Vol 173 ◽

pp. 564-570 ◽

Cited By ~ 18

Author(s):

Ying Yang ◽

Xue Yang ◽

Huipeng Li ◽

Chenzi Li ◽

Huaqian Ding ◽

...

Keyword(s):

Breast Tumor ◽

Near Infrared ◽

Tumor Therapy ◽

Infrared Light ◽

Near Infrared Light

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Mitochondria-acting carrier-free nanoplatform self-assembled by α-tocopheryl succinate carrying cisplatin for combinational tumor therapy

Regenerative Biomaterials ◽

10.1093/rb/rbab029 ◽

2021 ◽

Vol 8 (4) ◽

Author(s):

Heng Mei ◽

Jing Li ◽

Shengsheng Cai ◽

Xuequan Zhang ◽

Wenqiang Shi ◽

...

Keyword(s):

Drug Loading ◽

Tumor Therapy ◽

Ros Generation ◽

Drug Conjugates ◽

Tocopheryl Succinate ◽

Carrier Free ◽

Negative Surface ◽

Inert Carrier ◽

Self Assembled

Abstract Unsatisfactory drug loading capability, potential toxicity of the inert carrier and the limited therapeutic effect of a single chemotherapy drug are all vital inhibitory factors of carrier-assisted drug delivery systems for chemotherapy. To address the above obstacles, a series of carrier-free nanoplatforms self-assembled by dual-drug conjugates was constructed to reinforce chemotherapy against tumors by simultaneously disrupting intratumoral DNA activity and inhibiting mitochondria function. In this nanoplatform, the mitochondria-targeting small-molecular drug, α-tocopheryl succinate (TOS), firstly self-assembled into nanoparticles, which then were used as the carrier to conjugate cisplatin (CDDP). Systematic characterization results showed that this nanoplatform exhibited suitable particle size and a negative surface charge with good stability in physicochemical environments, as well as pH-sensitive drug release and efficient cellular uptake. Due to the combined effects of reactive oxygen species (ROS) generation by TOS and DNA damage by CDDP, the developed nanoplatform could induce mitochondrial dysfunction and elevated cell apoptosis, resulting in highly efficient anti-tumor outcomes in vitro. Collectively, the combined design principles adopted for carrier-free nanodrugs construction in this study aimed at targeting different intracellular organelles for facilitating ROS production and DNA disruption can be extended to other carrier-free nanodrugs-dependent therapeutic systems.

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