Tunable self-assembly of Irinotecan-fatty acid prodrugs with increased cytotoxicity to cancer cells

Zhang, Chunqiu; Jin, Shubin; Xue, Xiangdong; Zhang, Tingbin; Jiang, Yonggang; Wang, Paul; Liang, Xing‐Jie

doi:10.1039/c6tb00612d

Cited by 48 publications

(37 citation statements)

References 35 publications

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“…High hydrophilic content always tends to afford filamentous structures, while lower hydrophilic content prefers rod-like or spherical structures. 45, 56, 57 As a result, uniform nanorods were obtained at higher HCPT to Ce6 ratios through the confinement of the core HPCT nanostructure with an energy minimization process. It has been reported that cylindrical nanostructures exhibit very good pharmacokinetics and efficiency in drug delivery even better than spherical ones because of their multiple endocytotic mechanisms, enhanced internalization rates and effective adhesion to cell surface.…”

Section: Resultsmentioning

confidence: 99%

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Carrier-free, self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo

et al. 2017

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Carrier-free nanodrugs formulated from supramolecular self-assembly of pure drug molecules have emerged as an innovative and promising strategy for tumor therapy. We report herein a new and simple method to directly assemble a small hydrophobic anticancer drug 10-Hydroxycamptothecin (HCPT) with a photosensitizer Chlorin e6 (Ce6) to form stable, discrete nanorods (NRs), which not only circumvent the extreme hydrophobicity of HCPT but also incorporate two different modalities into one delivery system for combination therapy. Different ratios of HCPT to Ce6 were evaluated to afford the optimal nanoformulation. The as-prepared HCPT/Ce6 NRs were fully characterized, indicating a relatively uniform size of about 360 nm in length and 135 nm in width, surface charge of about −33 mV. Efficient internalization of the NRs by cancer cells was observed by confocal microscope and the generation of singlet oxygen species arising from the NRs under 655 nm laser irradiation was detected by DCFH-DA. As a result, very potent in vitro efficacy against several kinds of cancer cell lines was achieved through chemo-photodynamic dual therapy. The in vivo tumor suppression effect of HCPT/Ce6 NRs was verified on a subcutaneous xenograft mouse model, achieving almost complete inhibition of the tumor growth, which may benefit from the superiority of nanomedicine and combination therapy. The rationale of this facile and green strategy for carrier-free nanodrug formulation via self-assembly approach might open up new opportunities for the development of combinatorial therapeutics for tumor.

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Section: Resultsmentioning

confidence: 99%

“…Take advantage of this emerging strategy, a few chemotherapeutic agents (e.g., paclitaxel, doxorubicin, SN38, curcumin) have reported to be formulated as PNDs for enhanced anticancer therapy. 40–45 There is no doubt that the rationale of PNDs has shown great promise to be regarded as next generation of anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Carrier-free, self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo

et al. 2017

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“…Hydrophobic anticancer drug irinotecan (Ir) was esterified with fatty acid with different alkyl chain lengths yielding a small library of irinotecan‐fatty acid prodrugs (Ir‐5 C, Ir‐8 C and Ir‐12 C) and subsequent self‐assembly in aqueous environment resulted into nanoformulation of Ir‐fatty acid units (Figure ) and are hydrolyzed by carboxyesterases . Nanoformulation resulted in higher hydrophilicity, enhanced drug loading capacity and higher level accumulation in cancer cells.…”

Section: Biomolecular Nanodrug Formulationsmentioning

confidence: 95%

Recent Advances in Nanoformulated Chemotherapeutic Drug Delivery (2015‐2019)

Dorababu¹

2019

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An attempt was made to summarize the chemotherapeutic drug formulations at nanoscale. The number of biocompatible materials like carbohydrates, proteins, peptides, chitosan, and other water soluble materials would enhance the hydrophilicity of chemotherapeutic drugs. Some of the formulations were responsible for the improved anticancer activity, drug loading capability, higher encapsulation efficiency etc. Nanodrug formulations were engineered in such a way that hydrophobic anticancer agents were transformed to possess hydrophilic features which would allow them to self‐assemble into nanodrug carriers and hence longer blood circulation times of drug, sustained drug release were achieved. Tumor cell targetability was also achieved by selectively conjugating biomolecules with anticancer drugs. Drug loaded nanovectors exhibited improved cytotoxic activities compared to free drug molecules. Few classes of nanoformulations possessing major advantages were described in this review. These classes of drug delivery system possess a greater number of advantages over the other drug delivery systems. The amphiphilicity was enhanced by the complexation of the drugs and supramolecular micellation. Combination of the two or more drugs was successfully experimented via nanoprecipitation methods. Synergistic enhancement of the cytotoxic activity and good tumor growth inhibition evident by the introduction of chemotherapeutic nanopharmacology and nanodrug delivery methods were explained.

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“…142 Similarly, a lipidated Irinotecan prodrug was developed by Liang and co-workers that demonstrated increased cytotoxicity in cancer cells. 143 A similar process was also used to develop cytarabine nanoparticles through the conjugation of hexanoic acid. This system exhibited an increased cellular uptake in comparison to the native drug, improving in vitro the cytotoxicity of the drug.…”

Section: Small Molecule Sapdsmentioning

confidence: 99%

Self-assembling prodrugs

et al. 2017

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Covalent modification of therapeutic compounds is a clinically proven strategy to devise prodrugs with enhanced treatment efficacies. This prodrug strategy relies on modified drugs that possess advantageous pharmacokinetic properties and administration routes over their parent drug. Self-assembling prodrugs represent an emerging class of therapeutic agents capable of spontaneously associating into well-defined supramolecular nanostructures in aqueous solutions. The self-assembly of prodrugs expands the functional space of conventional prodrug design, providing a possible pathway to more effective therapies as the assembled nanostructure possesses distinct physicochemical properties that can be tailored to specific administration routes and disease treatment. In this review, we will discuss the various types of self-assembling prodrugs in development, providing an overview of the methods used to control their structure and function and, ultimately, our perspective on their current and future potential.

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Tunable self-assembly of Irinotecan-fatty acid prodrugs with increased cytotoxicity to cancer cells

Cited by 48 publications

References 35 publications

Carrier-free, self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo

Carrier-free, self-assembled pure drug nanorods composed of 10-hydroxycamptothecin and chlorin e6 for combinatorial chemo-photodynamic antitumor therapy in vivo

Recent Advances in Nanoformulated Chemotherapeutic Drug Delivery (2015‐2019)

Self-assembling prodrugs

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