Protein-Based Nanomedicine for Therapeutic Benefits of Cancer

Zhang, Liqun; Zhang, Junmin; Song, Jun; Liu, Yizhen; Ren, Xiangzhong; Zhao, Yanli

doi:10.1021/acsnano.1c00476

Cited by 74 publications

(62 citation statements)

References 357 publications

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“…It is worth noting that nanocarriers may help overcome drug resistance of cancers through multiple mechanisms, including enhancing drug uptake and increasing drugs retention time inside tumor cells 10 - 14 . Among the various nanoencapsulation strategies, protein nanocarrier possesses advantages in potential clinical application for being water-soluble, biocompatible, biodegradable, and non-toxic 6 , 15 , 16 . Currently, hydrophobic drugs are usually bound to the surface of proteins or protein particles via electrostatic interactions, which may cause instability of the colloidal system.…”

Section: Introductionmentioning

confidence: 99%

Re-engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy

Wang¹,

Zhao²,

Zhang³

et al. 2022

Theranostics

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Rationale: With the advantages of tumor-targeting, pH-responsive drug releasing, and biocompatibility, ferritin nanocage emerges as a promising drug carrier. However, its wide applications were significantly hindered by the low loading efficiency of hydrophobic drugs. Herein, we redesigned the inner surface of ferritin drug carrier (ins-FDC) by fusing the C- terminus of human H ferritin (HFn) subunit with optimized hydrophobic peptides. Methods: Hydrophobic and hydrophilic drugs were encapsulated into the ins-FDC through the urea-dependent disassembly/reassembly strategy and the natural drug entry channel of the protein nanocage. The morphology and drug loading/releasing abilities of the drug-loaded nanocarrier were then examined. Its tumor targeting character, system toxicity, application in synergistic therapy, and anti-tumor action were further investigated. Results: After optimization, 39 hydrophobic Camptothecin and 150 hydrophilic Epirubicin were encapsulated onto one ins-FDC nanocage. The ins-FDC nanocage exhibited programed drug release pattern and increased the stability and biocompatibility of the loaded drugs. Furthermore, the ins-FDC possesses tumor targeting property due to the intrinsic CD71-binding ability of HFn. The loaded drugs may penetrate the brain blood barrier and accumulate in tumors in vivo more efficiently . As a result, the drugs loaded on ins-FDC showed reduced side effects and significantly enhanced efficacy against glioma, metastatic liver cancer, and chemo-resistant breast tumors. Conclusions: The ins-FDC nanocarrier offers a promising novel means for the delivery of hydrophobic compounds in cancer treatments, especially for the combination therapies that use both hydrophobic and hydrophilic chemotherapeutics.

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Section: Introductionmentioning

confidence: 99%

Re-engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy

Wang¹,

Zhao²,

Zhang³

et al. 2022

Theranostics

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“…Furthermore, the nanoparticles showed selective killing of tumor cells and negligible toxicity towards normal cells. It has been previously shown that catalase could catalase could enhance the effect of photodynamic therapy on tumors 108 . Adamantane-modified chlorin e6 (Ada-Ce6) could be assembled with β-CD-grafted hyaluronic acid (HA-CD) to form nanoparticles, which could co-deliver catalase to tumor cells (Figure 7 d) 106 .…”

Section: Co-transport Of Protein and Othersmentioning

confidence: 99%

Multifunctional co-transport carriers based on cyclodextrin assembly for cancer synergistic therapy

Yi¹,

Liao²,

Zhao³

et al. 2022

Theranostics

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In the past few years, drug delivery systems have been used extensively to improve solubility, stability, and pharmacokinetics of chemotherapeutic drugs. However, traditional delivery systems fail to fulfill the required standard of effectiveness, primarily owing to issues of drug resistance exhibited by cancer cells and inherent differences among the patients. In this regard, combination therapy offers advantages of synergistic mechanism, reduced drug dosage, and enhanced therapeutic effect, which can be effectively utilized for the treatment of cancer. However, different types of therapeutic agents exhibit different pharmacokinetic properties and action targets in vivo , which lead to uncontrollable concentration ratio of therapeutic agents at the lesion site. This in turn causes serious side effects and affects synergistic anticancer effect. Importantly, multifunctional co-delivery systems are characterized by good pharmacokinetic properties, ability to provide targeted delivery, and controlled release in response to tumor microenvironment. Such delivery systems are widely used for co-delivery of therapeutic agents, which further assist in obtaining better synergistic anticancer effect, and can be potentially used for clinical application. Multifunctional co-delivery systems often exhibit complex structures and construction process. Since cyclodextrin is characterized by self-assembly property, it is possible to quickly construct cyclodextrin-based multifunctional co-delivery systems, with convenience and flexibility. The application of cyclodextrin in the construction of multifunctional co-delivery systems for cancer therapy has gained immense attention in the past few years. The present study provided overview of latest progress in the field of cyclodextrin-based multifunctional co-delivery systems for cancer synergistic therapy.

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“…Finally, while antibodies are most commonly associated with antigen targeting, ADCs are also being developed to conjugate cytotoxic drugs to tumor-specific receptor ligands. While these targeting modalities are not covered in this review, we point readers to these recently published reviews [191][192][193][194][195].…”

Section: Novel Target Antigensmentioning

confidence: 99%

Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective

et al. 2021

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Antibody-drug conjugates (ADCs) appear to be in a developmental boom, with five FDA approvals in the last two years and a projected market value of over $4 billion by 2024. Major advancements in the engineering of these novel cytotoxic drug carriers have provided a few early success stories. Although the use of these immunoconjugate agents are still in their infancy, valuable lessons in the engineering of these agents have been learned from both preclinical and clinical failures. It is essential to appreciate how the various mechanisms used to engineer changes in ADCs can alter the complex pharmacology of these agents and allow the ADCs to navigate the modern-day therapeutic challenges within oncology. This review provides a global overview of ADC characteristics which can be engineered to alter the interaction with the immune system, pharmacokinetic and pharmacodynamic profiles, and therapeutic index of ADCs. In addition, this review will highlight some of the engineering approaches being explored in the creation of the next generation of ADCs.

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Protein-Based Nanomedicine for Therapeutic Benefits of Cancer

Cited by 74 publications

References 357 publications

Re-engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy

Re-engineering the inner surface of ferritin nanocage enables dual drug payloads for synergistic tumor therapy

Multifunctional co-transport carriers based on cyclodextrin assembly for cancer synergistic therapy

Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective

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