Somatostatin Receptor–Mediated Specific Delivery of Paclitaxel Prodrugs for Efficient Cancer Therapy

Huo, Meirong; Zhu, Qinnv; Wu, Qu; Yin, Tingjie; Wang, Lei; Yin, Lifang; Zhou, Jianping

doi:10.1002/jps.24438

Cited by 21 publications

(20 citation statements)

References 35 publications

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“…Our group has previously developed the OCT(Phe)-PEG-PTX prodrug delivery system and obtained enhanced antitumor efficiency compared to that of mPEG-PTX and Taxol due to the active targeting ability enabled by OCT. However, in agreement with the drug release behavior of general prodrug conjugates fabricated from ester bonds, the full drug release of the OCT(Phe)-PEG-PTX prodrug was sustained more than 180 h. 20 The amount of liberated drug below the effective dose would lead to a reduced drug efficacy. To achieve triggered drug release within tumor cells, stimuli including external signals (magnetic field, 21 temperature, 22 ultrasound, 23 light, 24 and electric current 25 ) as well as physiological signals (enzymes, 26 pH, 27 and redox potential 28 ) have been widely applied in drug delivery systems (DDSs).…”

Section: Introductionsupporting

confidence: 53%

“…The OCT(Phe)-PEG-NH 2 active molecules was synthesized and purified as we previously reported. 20 Briefly, NHS-PEG-NH-Boc was conjugated with OCT followed by purification by a reversed-phase high-performance liquid chromatography (HPLC) system to obtain OCT(Phe)-PEG-NH-Boc. Finally, the OCT(Phe)-PEG-NH-Boc was deprotected to get OCT(Phe)-PEG-NH 2 .…”

Section: Introductionmentioning

confidence: 99%

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Well-Defined Redox-Sensitive Polyethene Glycol–Paclitaxel Prodrug Conjugate for Tumor-Specific Delivery of Paclitaxel Using Octreotide for Tumor Targeting

Yin

Wang

et al. 2015

Mol. Pharmaceutics

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A redox-sensitive prodrug, octreotide(Phe)-polyethene glycol-disulfide bond-paclitaxel [OCT(Phe)-PEG-ss-PTX], was successfully developed for targeted intracellular delivery of PTX. The formulation emphasizes long-circulation-time polymer-drug conjugates, combined targeting based on EPR and OCT-receptor mediated endocytosis, sharp redox response, and programmed drug release. The nontargeted redox-sensitive prodrug, mPEG-ss-PTX, and the targeted insensitive prodrug, OCT(Phe)-PEG-PTX, were also synthesized as controls. These polymer-PTX conjugates, structurally confirmed by 1H NMR, exhibited approximately 23,000-fold increase in water solubility over parent PTX and possessed drug contents ranging from 11% to 14%. The redox-sensitivity of the objective OCT(Phe)-PEG-ss-PTX prodrug was verified by in vitro PTX release profile in simulated reducing conditions, and the SSTRs-mediated endocytosis was demonstrated by flow cytometry and confocal laser scanning microscopy analyses. Consequently, compared with mPEG-PTX and OCT(Phe)-PEG-PTX, the OCT(Phe)-PEG-ss-PTX exhibited much stronger cyotoxicity and apoptosis-inducing ability against NCI-H446 tumor cells (SSTRs overexpression), whereas a comparable cytotoxicity of these prodrugs was obtained against WI-38 normal cells (no SSTRs expression). Finally, the in vivo studies on NCI-H466 tumor-bearing nude mice demonstrated that the OCT(Phe)-PEG-ss-PTX possessed superior tumor-targeting ability and antitumor activity over mPEG-PTX, OCT(Phe)-PEG-PTX and Taxol, as well as minimal collateral damage. This targeted redox-sensitive polymer-PTX prodrug system is promising in tumor therapy.

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Section: Introductionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Well-Defined Redox-Sensitive Polyethene Glycol–Paclitaxel Prodrug Conjugate for Tumor-Specific Delivery of Paclitaxel Using Octreotide for Tumor Targeting

Yin

Wang

et al. 2015

Mol. Pharmaceutics

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“…The studies have revealed that a mixture of products (modification at the N-terminus, the lysine residue, or both) was produced when octreotide was allowed to react with NHS esters. [27][28][29][30] Octreotide was treated with compound 7 (3 eq.) in the presence of Et 3 N (6 eq.)…”

Section: Resultsmentioning

confidence: 99%

Selective lysine modification of native peptides via aza-Michael addition

Chen

Huang

et al. 2017

Org. Biomol. Chem.

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A series of vinylsulfonamides were synthesized and screened for site-selective modification of the ε-amino group of lysine-bearing free α-amine residues. N-Methyl-N-phenylethenesulfonamide has emerged as an applicable reagent and has been developed for efficient and highly selective modification of the lysine residue of native peptides in the presence of a free N-terminus via aza-Michael addition. We demonstrated that functional N-phenylvinylsulfonamide derivatives with a fluorescent moiety or drug could also be conjugated to the lysine residue of octreotide and insulin with high specificity, without modifying the N-terminus. Our method provides a promising strategy for site-selective lysine functionalization in native peptides with a free N-terminus.

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“…Ligands are typically selected to bind surface molecules or receptors over-expressed in diseased organs, tissues, cells or subcellular domains [1]. Examples include prostate specific membrane antigen (PSMA) [3], somatostatin receptor (SSTR) [23,24] or folate receptor (FR) among others [1,25]. While early animals studies often show convincing differences in tumor accumulation between targeted and non-targeted preparations (or target expressing tumors vs non-expressers), on average the benefit of targeting is highly heterogeneous [12], highly dependent on the tumor model and tissue type [26], and clinical results are often not strongly convincing [8,27–29].…”

Section: Introductionmentioning

confidence: 99%

Imaging the pharmacology of nanomaterials by intravital microscopy: Toward understanding their biological behavior

Miller

Weissleder

2017

Advanced Drug Delivery Reviews

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Therapeutic nanoparticles (NPs) can deliver cytotoxic chemotherapeutics and other drugs more safely and efficiently to patients; furthermore, selective delivery to target tissues can theoretically be accomplished actively through coating NPs with molecular ligands, and passively through exploiting physiological “enhanced permeability and retention” features. However, clinical trial results have been mixed in showing improved efficacy with drug nano-encapsulation, largely due to heterogeneous NP accumulation at target sites across patients. Thus, a clear need exists to better understand why many NP strategies fail in vivo and not result in significantly improved tumor uptake or therapeutic response. Multicolor in vivo confocal fluorescence imaging (intravital microscopy; IVM) enables integrated pharmacokinetic and pharmacodynamic (PK/PD) measurement at the single-cell level, and has helped answer key questions regarding the biological mechanisms of in vivo NP behavior. This review summarizes progress to date and also describes useful technical strategies for successful IVM experimentation.

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Somatostatin Receptor–Mediated Specific Delivery of Paclitaxel Prodrugs for Efficient Cancer Therapy

Cited by 21 publications

References 35 publications

Well-Defined Redox-Sensitive Polyethene Glycol–Paclitaxel Prodrug Conjugate for Tumor-Specific Delivery of Paclitaxel Using Octreotide for Tumor Targeting

Well-Defined Redox-Sensitive Polyethene Glycol–Paclitaxel Prodrug Conjugate for Tumor-Specific Delivery of Paclitaxel Using Octreotide for Tumor Targeting

Selective lysine modification of native peptides via aza-Michael addition

Imaging the pharmacology of nanomaterials by intravital microscopy: Toward understanding their biological behavior

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