Enzyme-responsive peptide dendrimer-gemcitabine conjugate as a controlled-release drug delivery vehicle with enhanced antitumor efficacy

Zhang, Chengyuan; Pan, Dayi; Li, Jin; Hu, Jiani; Bains, Ashika; Guys, Nicholas; Zhu, Hongyan; Li, Xiaohui; Luo, Kui; Gong, Qiyong; Gu, Zhongwei

doi:10.1016/j.actbio.2017.02.047

Cited by 143 publications

(71 citation statements)

References 48 publications

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“…On the other hand, tumor‐penetrating peptides are designed to target only cancer cells, which express cancer‐related antigens. Tumor‐penetrating peptides can efficiently bind to tumor receptors, but they can also penetrate deep into tumor tissues, which makes them very useful for targeted drug delivery and the chemotherapy of solid tumors . Another advancement in PDCs is their low immunogenicity, as these prodrugs generally have short peptide chains that do not trigger undesired autoimmune responses .…”

Section: Peptide–drug Conjugatesmentioning

confidence: 99%

Protease‐activated prodrugs: strategies, challenges, and future directions

Poręba

2020

The FEBS Journal

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Proteases play critical roles in virtually all biological processes, including proliferation, cell death and survival, protein turnover, and migration. However, when dysregulated, these enzymes contribute to the progression of multiple diseases, with cancer, neurodegenerative disorders, inflammation, and blood disorders being the most prominent examples. For a long time, disease-associated proteases have been used for the activation of various prodrugs due to their well-characterized catalytic activity and ability to selectively cleave only those substrates that strictly correspond with their active site architecture. To date, versatile peptide sequences that are cleaved by proteases in a site-specific manner have been utilized as bioactive linkers for the targeted delivery of multiple types of cargo, including fluorescent dyes, photosensitizers, cytotoxic drugs, antibiotics, and pro-antibodies. This platform is highly adaptive, as multiple protease-labile conjugates have already been developed, some of which are currently in clinical use for cancer treatment. In this review, recent advancements in the development of novel protease-cleavable linkers for selective drug delivery are described. Moreover, the current limitations regarding the selectivity of linkers are Abbreviations AAC, antibody-antibiotic conjugate; Ab, antibody; ACC, 7-amino-4-carbamoylmethylcoumarin; ADAM, a disintegrin and metalloproteinase; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; ADC, antibody-drug conjugate; aPSs, activatable photosensitizers; BHQ-3, black hole quencher 3; Boc, tert-butyloxycarbonyl group; BT20, a type of mammary gland carcinoma; Cas9, CRISPR-associated protein 9;

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Section: Peptide–drug Conjugatesmentioning

confidence: 99%

Protease‐activated prodrugs: strategies, challenges, and future directions

Poręba

2020

The FEBS Journal

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“…The nanoparticle showed significantly rapid GEM release in the secreted Cathepsin B environment, compared with conditions without Cathepsin B. This dendrimer–GEM nanoparticle displayed enhanced antitumor efficacy in a 4T1 murine breast cancer model, with minimal toxicity; twofold higher tumor growth inhibition was induced by the dendrimer–GEM nanoparticle than by free GEM (Zhang, Pan, et al, 2017). …”

Section: Stimuli-responsive Drug Deliverymentioning

confidence: 99%

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

Amreddy

Babu

Muralidharan

et al. 2018

Advances in Cancer Research

235

145

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Effective and safe delivery of anticancer agents is among the major challenges in cancer therapy. The majority of anticancer agents are toxic to normal cells, have poor bioavailability, and lack in vivo stability. Recent advancements in nanotechnology provide safe and efficient drug delivery systems for successful delivery of anticancer agents via nanoparticles. The physicochemical and functional properties of the nanoparticle vary for each of these anticancer agents, including chemotherapeutics, nucleic acid-based therapeutics, small molecule inhibitors, and photodynamic agents. The characteristics of the anticancer agents influence the design and development of nanoparticle carriers. This review focuses on strategies of nanoparticle-based drug delivery for various anticancer agents. Recent advancements in the field are also highlighted, with suitable examples from our own research efforts and from the literature.

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“…This study demonstrated that control on spatial distribution and/or temporal release of DEX can be achieved using a dendrimer‐based gel formulation. Furthermore, control on spatiotemporal drug release from dendrimer‐based delivery systems can be achieved by fabrication of stimuli‐responsive or bioreducible dendrimers (Eghtesadi et al, ; C. Zhang, Pan, et al, ; D. Zhong et al, ). Although such on‐demand DDS have not been explored for ophthalmic applications, they can be useful for the effective treatment of specific ocular diseases.…”

Section: Ocular Drug Delivery Systemsmentioning

confidence: 99%

“…Although such on‐demand DDS have not been explored for ophthalmic applications, they can be useful for the effective treatment of specific ocular diseases. Hence, dendrimer‐based DDS can be used as promising carriers to enhance ocular permeability, intraocular/cellular retention, and to enable controlled drug release of topically or intraocularly administered drugs (Eghtesadi et al, ; C. Zhang, Pan, et al, ; D. Zhong et al, ).…”

Section: Ocular Drug Delivery Systemsmentioning

confidence: 99%

Fundamentals, challenges, and nanomedicine‐based solutions for ocular diseases

Srinivasarao

Lohiya

Katti

2018

WIREs Nanomed Nanobiotechnol

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The eye consists of sensitive, compactly adjoined tissue structures which act as strong physical (static) and physiological (dynamic) barriers that prevent entry of foreign bodies into the eye. Together, these barriers reduce the bioavailability of topically and intraocularly administered medicaments thus demanding frequent drug administration for the treatment of chronic eye diseases. Hence, development of drug delivery systems (DDS) that can be retained in ocular tissues for longer durations can help to reduce the frequency of drug administration, whereas, delivery systems that traverse through ocular barriers may offer higher bioavailability of administered drugs to otherwise inaccessible ocular tissues. These objectives can be partially/fully achieved using nanoparticulate/colloidal DDS. Colloidal DDS, due to their nanodimensions, undergo internalization by cells which enables transport of drugs through ocular barriers. Furthermore, nanoparticles can prolong duration of drug release and can increase residence time of entrapped cargo molecules in ocular tissues. Together, these aspects facilitate a higher bioavailability, prolonged therapeutic effect and reduced frequency of drug administration for the effective treatment of chronic ocular diseases. Hence, nanocarriers have been widely explored for ophthalmic drug delivery applications. In this review, we discuss the anatomy of ocular tissues along with their barrier properties. We then discuss ocular diseases along with the various routes of drug administration and pathways of drug transport in the eye. The next section discusses the influence of physicochemical properties of therapeutic molecules on their ocular distribution and conventional and advanced (nanoparticulate/colloidal DDS) drug formulations that are used for the treatment of ocular diseases.

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Enzyme-responsive peptide dendrimer-gemcitabine conjugate as a controlled-release drug delivery vehicle with enhanced antitumor efficacy

Cited by 143 publications

References 48 publications

Protease‐activated prodrugs: strategies, challenges, and future directions

Protease‐activated prodrugs: strategies, challenges, and future directions

Recent Advances in Nanoparticle-Based Cancer Drug and Gene Delivery

Fundamentals, challenges, and nanomedicine‐based solutions for ocular diseases

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