Small Molecules for Active Targeting in Cancer

Kue, Chin Siang; Kamkaew, Anyanee; Burgess, Kevin; Kiew, Lik Voon; Chung, Lip Yong; Lee, Hong B.

doi:10.1002/med.21387

Cited by 111 publications

(98 citation statements)

References 314 publications

(352 reference statements)

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“…This change was significantly higher when NPs were synthesized using a high molecular weight HA-NH 2 (1 MDa). To take advantage of the EPR effect, NPs need to be smaller than 800 nm [34], so the hydrodynamic radius was a big concern. To address this issue, we selected a smaller HA-NH 2 (10 kDa) to obtain smaller NPs in solution.…”

Section: Resultsmentioning

confidence: 99%

Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces Apoptosis in Cancer Cells

Cm¹,

Bn²,

Am³

et al. 2017

J Nanomed Nanotechnol

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Herein we tested a nanosized cancer-cell targeted delivery system based on cytochrome c (Cyt c) and hyaluronic acid. Cyt c was chosen since it is a per se non-toxic protein but causes apoptosis when delivered to the cytoplasm of target cells. Hyaluronic acid was employed to create the nanosized delivery system with passive targeting capability in order to exploit the enhanced permeation and retention (EPR) effect and active targeting capability of hyaluronic acid. In addition, our goal was to incorporate a smart release strategy to only promote protein release upon reaching its target.Nanoparticles were formed by a simple yet precise nanoprecipitation process based on desolvation. They were physically characterized to select precipitation conditions leading to adequate size, shape, protein bioactivity, and protein loading to produce a feasible targeted cancer treatment. We synthesized nanoparticles of around 500 nm diameter with a 60% protein loading and more than 80% of protein bioactivity. In vitro, cumulative release of 92% of Cyt c was observed after 8 h under conditions mimicking the reductive intracellular environment, while under non-denaturing conditions only 20% was released. The nanoparticles displayed a selective cytotoxic effect on cancer cells. After 6 h of incubation with the nanoparticles, hyaluronic acid receptor over expressing A549 human lung adenocarcinoma cells showed a viability of ca. 20% at 0.16 mg/ml of Cyt c concentration. Only a negligible effect was observed on viability of COS-7 African green monkey kidney fibroblast, a normal cell line notoverexpressing the hyaluronic acid receptor. Confocal microscopy confirmed that the drug delivery system indeed delivered Cyt c to the cytoplasm of the target cells. We conclude that we were able to create a smart stimuli-responsive targeted drug delivery system with significant potential in cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces Apoptosis in Cancer Cells

Cm¹,

Bn²,

Am³

et al. 2017

J Nanomed Nanotechnol

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“…The structure of this kind of drug delivery system generally includes a targeting moiety linked to a potent chemotherapeutic drug via a linker that embodies a cleavable bond. 292 The above-mentioned targeted delivery strategies have provided great advantages over traditional non-targeted chemotherapeutic drugs. 292 However, the progression and treatment of tumors involves many complicated stages including initiation, progression, metastasis, recurrence, and resistance to therapy.…”

Section: Challenges and Perspectives For Optical Chemical Probesmentioning

confidence: 99%

“…292 The above-mentioned targeted delivery strategies have provided great advantages over traditional non-targeted chemotherapeutic drugs. 292 However, the progression and treatment of tumors involves many complicated stages including initiation, progression, metastasis, recurrence, and resistance to therapy. A precise diagnosis is indispensable for tumor staging and early therapy.…”

Section: Challenges and Perspectives For Optical Chemical Probesmentioning

confidence: 99%

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

et al. 2017

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Surgical resection of solid tumors is currently the gold standard and preferred therapeutic strategy for cancer. Chemotherapy drugs also make a significant contribution by inhibiting the rapid growth of tumor cells and these two approaches are often combined to enhance treatment efficacy. However, surgery and chemotherapy inevitably lead to severe side effects and high systemic toxicity, which in turn results in poor prognosis. Precision medicine has promoted the development of treatment modalities that are developed to specifically target and kill tumor cells. Advances in in vivo medical imaging for visualizing tumor lesions can aid diagnosis, facilitate surgical resection, investigate therapeutic efficacy, and improve prognosis. In particular, the modality of fluorescence imaging has high specificity and sensitivity and has been utilized for medical imaging. Therefore, there are great opportunities for chemists and physicians to conceive, synthesize, and exploit new chemical probes that can image tumors and release chemotherapy drugs in vivo. This review focuses on small molecular ligand-targeted fluorescent imaging probes and fluorescent theranostics, including their design strategies and applications in clinical tumor treatment. The progress in chemical probes described here suggests that fluorescence imaging is a vital and rapidly developing field for interventional surgical imaging, as well as tumor diagnosis and therapy.

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“…The polymeric NPs can further be conjugated with targeting agents such as folic acid (FA), antibody (Ab), peptide (e.g., RGD), or aptamer (Ap), and/or imaging agents such as gold NPs (AuNPs), quantum dots (QDs), magnetic NPs (MNPs) and carbon nanotubes (CNTs). Such functionalization makes them multifunctional NSs with great potential in simultaneous targeting, imaging, and therapy of diseases …”

Section: Introductionmentioning

confidence: 99%

Chitosan‐based multifunctional nanomedicines and theranostics for targeted therapy of cancer

Fathi

Majidi

Zangabad

et al. 2018

Medicinal Research Reviews

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Nanotechnology as an emerging field has established inevitable impacts on nano-biomedicine and treatment of formidable diseases, inflammations, and malignancies. In this regard, substantial advances in the design of systems for delivery of therapeutic agents have emerged magnificent and innovative pathways in biomedical applications. Chitosan (CS) is derived via deacetylation of chitin as the second most abundant polysaccharide. Owing to the unique properties of CS (e.g., biocompatibility, biodegradability, bioactivity, mucoadhesion, cationic nature and functional groups), it is an excellent candidate for diverse biomedical and pharmaceutical applications such as drug/gene delivery, transplantation of encapsulated cells, tissue engineering, wound healing, antimicrobial purposes, etc. In this review, we will document, discuss, and provide some key insights toward design and application of miscellaneous nanoplatforms based on CS. The CS-based nanosystems (NSs) can be employed as advanced drug delivery systems (DDSs) in large part due to their remarkable physicochemical and biological characteristics. The abundant functional groups of CS allow the facile functionalization in order to engineer multifunctional NSs, which can simultaneously incorporate therapeutic agents, molecular targeting, and diagnostic/imaging capabilities in particular against malignancies. These multimodal NSs can be literally translated into clinical applications such as targeted diagnosis and therapy of cancer because they offer minimal systemic toxicity and maximal cytotoxicity against cancer cells and tumors. The recent developments in the CS-based NSs functionalized with targeting and imaging agents prove CS as a versatile polymer in targeted imaging and therapy.

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Small Molecules for Active Targeting in Cancer

Cited by 111 publications

References 314 publications

Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces Apoptosis in Cancer Cells

Smart Release Nano-formulation of Cytochrome C and Hyaluronic Acid Induces Apoptosis in Cancer Cells

Fluorescent chemical probes for accurate tumor diagnosis and targeting therapy

Chitosan‐based multifunctional nanomedicines and theranostics for targeted therapy of cancer

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