Natural and synthetic nanovectors for cancer therapy

Abstract

Nanomaterials have been extensively studied in cancer therapy as vectors that may improve drug delivery. Such vectors not only bring numerous advantages such as stability, biocompatibility, and cellular uptake but have also been shown to overcome some cancer-related resistances. Nanocarrier can deliver the drug more precisely to the specific organ while improving its pharmacokinetics, thereby avoiding secondary adverse effects on the not target tissue. Between these nanovectors, diverse material types can be discerned, such as liposomes, dendrimers, carbon nanostructures, nanoparticles, nanowires, etc., each of which offers different opportunities for cancer therapy. In this review, a broad spectrum of nanovectors is analyzed for application in multimodal cancer therapy and diagnostics in terms of mode of action and pharmacokinetics. Advantages and inconveniences of promising nanovectors, including gold nanostructures, SPIONs, semiconducting quantum dots, various nanostructures, phospholipid-based liposomes, dendrimers, polymeric micelles, extracellular and exome vesicles are summarized. The article is concluded with a future outlook on this promising field.

Keywords: Nanoparticles; cancer; drug delivery; nanomaterials; nanovectors.

Figure 1

Overview of the scope of the article

Figure 2

(A) Illustration of a super stealth liposome (SSL). The stability of the vesicle has been enhanced by attaching a single polyethylene glycol (PEG) chain to several phospholipids. When used as a drug delivery vehicle, this SSL exhibits a better biodistribution and antitumour effect than conventional stealth liposomes (SLs). The plot quantifies the stability of SSLs in serum. The leakage of ³[H]CHE from the SL and SSLs was used as a stability measurement. (B) Confocal laser scanning micrographs of CaCo-2 cells incubated with fluorescein-labelled SL and SSLs. CaCo-2 cells were treated with fluorescent SL or SSLs and incubated for different periods (1 h, 6 h, 12 h, and 24 h). a, SL. b, SSL_{. c, SSL. d, SSL. e, Control (untreated CaCo-2 cells). Modified and reproduced with permission . Reproduced with permission. Copyright Elsevier (2015).}

Figure 3

A suggested model for the cellular uptake of (A) poly(amidoamine) (PAMAM)-amide-doxorubicin and (B) PAMAM-hydrazone-doxorubicin in light-exposed Ca9-22 cells. Nuclear accumulation of doxorubicin is denoted by arrows . Reproduced with permission. Copyright Elsevier (2007).

Figure 4

In vivo treatment of tumour-carrying mice treated with phosphate-buffered saline (PBS), G5.NHAc-PEG-PBA (GPP), G5.NHAc-PEG-PBA@Cu(II) (GPPC), G5.NHAc-PEG-PBA@Cu(II)/TPZ(CPPCT), G5.NHAc-mPEG@Cu(II)/TPZ (GmPCT), or tirapazamine (TPZ). (a) Treatment strategy. (b) Body weight. (c) Relative tumour volume. (d) Tumour weight . Reproduced with permission. Copyright Springer (2022).

Figure 5

The temperature-responsive micelle-based delivery system for co-delivery genes and anticancer drugs . Reproduced with permission. Copyright Wiley (2015).

Figure 6

Carbon nanotube conjugated to CpG (CNT-CpG) inhibits the transforming growth factor-beta (TGF-β)-induced epithelial-to-mesenchymal transition (EMT) of colon cancer cells. (a) Morphological alterations in HCT116 cells. (b) Treated cells were stained with DAPI and an anti-SMAD2/3 antibody. (c and d) Messenger RNA (mRNA) and protein expression of EMT marker genes were detected by real-time polymerase chain reaction and western blot, respectively . Reproduced with permission. Copyright Wolters Kluwer Health (2020).

Figure 7

The use of gold nanoparticles (AuNPs) to enhance the lethal impact of X-rays on tumour tissue. (A) A micrograph of spherical AuNPs. (B) The clonogenic assay showed that the largest effect occurred with 50-nm AuNPs. (C) Confocal micrograph showing the uptake of AuNPs. (D-F) Increased radiosensitization of Graphene nanoribbons (GNRs) in vitro in prostate cancer cell lines and in vivo by measuring the tumour volume. Reproduced with permission from . Copyright Elsevier, 2015.

Figure 8

Construction of a multi-component cancer treatment agent based on MSNs depicted in the top left corner. (B) The mechanism of action in vivo. Reproduced with permission from . Copyright American Chemical Society (2016).

Figure 9

Generation of bio-compatible SPIONs and their interaction with cells. Abbreviations: Fe₃O₄ NPs, superparamagnetic iron oxide nanoparticles; IR, irinotecan; LA-IR, amphiphilic lauric acid-irinotecan prodrug; SPIO@IR, LA-IR inserted SPIO prodrug. Reproduced with permission from . Copyright Royal Society of Chemistry (2018).

Figure 10

The multi-color imaging of fixed human epithelial cells using five types of QDs. Adapted with permission . Copyright Springer (2015).

Figure 11

(A) formation of gold nanosphere-based agent, (B) determination of size by dynamic light scattering, (C) TEM micrographs of the obtained material. Adapted with permission . Copyright Wiley (2013).

Figure 12

Chemo/photothermal therapy by engineered extracellular vesicles (EVs) that co-deliver drugs and photothermal agents (PTAs) to tumour sites . Reproduced with permission. Copyright Springer (2022).

Figure 13

Engineered mesenchymal stem cell exosomes (MSC-EXs) for cancer treatment. These structures carry microRNAs (miRNAs), small-molecule drugs, and proteins . Reproduced with permission. Copyright Hindawi (2021).

Figure 14

Typical properties and anticancer implementation of natural killer (NK) cell-derived extracellular vesicles (EVs). NK EVs bind cancer cells via NKG2D-MICA/B and promote cytotoxicity by releasing their cytotoxic protein cargo. In addition, engineered NK EV-coated nanoparticles have been used to deliver anticancer agents . Reproduced with permission. Copyright Frontiers (2021).

Figure 15

Characterization of plasma membrane-coated grapefruit-derived nanovectors (IGNVs) characterization. (A) Preparation and drug loading steps. (B) Surface zeta potential measurement. (C) Scanning electron microscopy free GNVs (top) and IGNVs (bottom). (D) Co-localisation of the EL4 cell-derived plasma membranes and GNV cores. (E) Fluorescence resonance energy transfer-based measurements of IGNV formation. Reproduced with permission. Copyright Elsevier (2019).