Multifunctional self-assembled peptide nanoparticles for multimodal imaging-guided enhanced theranostic applications against glioblastoma multiforme

Rizvi, Syed Faheem Askari; Ali, Azam; Ahmad, M.; Mu, Shuai; Zhang, Haixia

doi:10.1039/d1na00597a

Cited by 7 publications

(6 citation statements)

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“…Additionally, the fluorescent/radioactive imaging properties of our novel-designed PDC were introduced in two-step reactions . First, the ε-amino group of the terminal lysine residue was covalently conjugated with carbonyl carbon of the near-infrared fluorescent (NIRF) dye cyanine 5.5 N -hydroxysuccinimide (NHS) ester to induce optical molecular imaging properties of PDC (Scheme , step 1) with a chemical purity of >95% as shown by UHPLC analysis ( R t = 8.360 min), while HR-MS analysis shows [M + H] + m / z : 2271.1069 a.m.u.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, the fluorescent/radioactive imaging properties of our novel-designed PDC were introduced in two-step reactions. 35 First, the ε-amino group of the terminal lysine residue was covalently conjugated with carbonyl carbon of the near-infrared fluorescent (NIRF) dye cyanine 5.5 N-hydroxysuccinimide (NHS) ester to induce optical molecular imaging properties of PDC (Scheme 2, step 1) with a chemical purity of >95% as shown by UHPLC analysis (R t = 8.360 min), while HR-MS analysis shows [M + H] + m/z: 2271.1069 a.m.u. In contrast, in the second reaction, the same ε-amino group of the terminal lysine residue was covalently conjugated with the deprotected β-carboxylic acid group of diethylenetriamine pentaacetic acid (DTPA) as a bifunctional chelating agent (BFCA) with a chemical purity of >97% (R t = 6.978 min), while HR-MS analysis shows [M + H] + m/z: 2079.2003 a.m.u.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Identification of a pH-Responsive Peptide–Paclitaxel Conjugate as a Novel Drug with Improved Therapeutic Potential

et al. 2023

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A highly sensitive, nontoxic, hydrophilic cell-penetrating peptide (CPP = c[RGDKLAK]) was selected for the construction of an effective peptide−drug conjugate (PDC). A hydrophobic drug paclitaxel (PTX) was successfully conjugated with CPP via ester linkage with succinic acid (SA) as a pH-cleavable linker moiety. The characterization techniques employed in this study indicate the >95% purity of the resulting PDC (CPP−SA−PTX). The in vitro studies show that our proposed PDC exhibits enhanced stability (∼90%) and cytotoxicity (EC 50 = 8.32 ± 0.09 nM). Besides the excellent solubility of PDC in water, the PTX effect on positive β-tubulin-III indicates that the drug releases retained pharmacological properties. Additionally, in vivo, therapeutic-dose treatment reveals the prominent tumor-growth inhibitory effects (2.82−3.24-fold) of PDC in tumor mice models. Subsequently, these observations confirmed that our novel-designed PDC (CPP−SA−PTX) adduct may serve as a promising therapeutic agent to treat glioblastoma.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Identification of a pH-Responsive Peptide–Paclitaxel Conjugate as a Novel Drug with Improved Therapeutic Potential

et al. 2023

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“…Interestingly, these SAPNs showed high affinity and cytotoxicity for α v β 3 -integrin overexpressed on glioblastoma (U87MG) cells with EC 50 = 20 μM/L, as well as enhanced apoptosis rate (≥80% at 24 h incubation), and multimodal (SPECT/Optical) diagnostic functionality. 151 Furthermore, the same group synthesized a novel radiotracer ( 99m Tc-DTPA-c[RGDKLAK]) and studied its efficacy to diagnose Alzheimer's disease preclinically. The results showed that radiotracer was highly accumulated in α v β 3integrin expressing brain region with decreased uptake in the liver and kidneys having target-to-nontarget ratio 28.47 ± 2.53 at 3 h postinjection.…”

Section: ■ Peptides For Drug Delivery Systemmentioning

confidence: 99%

Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic

Rizvi,

Zhang,

Zhang

et al. 2024

ACS Pharmacol. Transl. Sci.

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The emergence of peptide−drug conjugates (PDCs) that utilize targetoriented peptide moieties as carriers of cytotoxic payloads, interconnected with various cleavable/noncleavable linkers, resulted in the key-foundation of the new era of targeted therapeutics. They are capable of retaining the integrity of conjugates in the blood circulatory system as well as releasing the drugs at the tumor microenvironment. Other valuable advantages are specificity and selectivity toward targeted-receptors, higher penetration ability, and drug-loading capacity, making them a suitable candidate to play their vital role as promising carrier agents. In this review, we summarized the types of cell-targeting (CTPs) and cell-penetrating peptides (CPPs) that have broad applications in the advancement of targeted drug-delivery systems (DDS). Moreover, the techniques to overcome the limitations of peptide-chemistry for their extensive implementation to construct the PDCs. Besides this, the diversified breakthrough of linker chemistry, and ample knowledge of various cytotoxic payloads used in PDCs in recent years, as well as the mechanism of action of PDCs was critically discussed. The principal aim is to provide scattered and diversified knowledge in one place and to help researchers understand the pinching knots in the science of PDC development, also their progression toward a bright future for PDCs as novel theranostics in clinical practice.

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“…Rizvi et al had developed a Cy5.5-conjugated self-assembled peptide nanoprobe Cy5.5@SAPD- 99m Tc based on a novel head-to-tail cyclic RGD-KLAK heptapeptide sequence. The effectiveness and efficacy of this probe for the diagnosis of glioblastoma multiforme had been proven in the tumor-bearing female Balb/c mice models guided by FI/SPECT imaging ( Rizvi et al, 2021 ).…”

Section: Bimodal Imaging Of Tumor Based On Near-infrared-i Fluorescencementioning

confidence: 99%

NIR-I Dye-Based Probe: A New Window for Bimodal Tumor Theranostics

et al. 2022

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Near-infrared (NIR, 650–1700 nm) bioimaging has emerged as a powerful strategy in tumor diagnosis. In particular, NIR-I fluorescence imaging (650–950 nm) has drawn more attention, benefiting from the high quantum yield and good biocompatibility. Since their biomedical applications are slightly limited by their relatively low penetration depth, NIR-I fluorescence imaging probes have been under extensive development in recent years. This review summarizes the particular application of the NIR-I fluorescent dye-contained bimodal probes, with emphasis on related nanoprobes. These probes have enabled us to overcome the drawbacks of individual imaging modalities as well as achieve synergistic imaging. Meanwhile, the application of these NIR-I fluorescence-based bimodal probes for cancer theranostics is highlighted.

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Multifunctional self-assembled peptide nanoparticles for multimodal imaging-guided enhanced theranostic applications against glioblastoma multiforme

Abstract: This study describes the development of self-assembled peptide nanoparticles with improved functionality via modifications by using multimodal imaging tools and enhanced the therapeutic efficacy against brain tumor glioblastoma multiforme.

Cited by 7 publications

References 50 publications

Identification of a pH-Responsive Peptide–Paclitaxel Conjugate as a Novel Drug with Improved Therapeutic Potential

Identification of a pH-Responsive Peptide–Paclitaxel Conjugate as a Novel Drug with Improved Therapeutic Potential

Peptide-Drug Conjugates: Design, Chemistry, and Drug Delivery System as a Novel Cancer Theranostic

NIR-I Dye-Based Probe: A New Window for Bimodal Tumor Theranostics

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