Background
In the last decade, graphene oxide-based nanomaterials, such as graphene oxide (GO) and reduced graphene oxide (rGO), have attracted more and more attention in the field of biomedicine. ...Due to the versatile surface functionalization, ultra-high surface area, and excellent biocompatibility of graphene oxide-based nanomaterials, which hold better promise for potential applications than among other nanomaterials in biomedical fields including drug/gene delivery, biomolecules detection, tissue engineering, especially in cancer treatment.
Results
Here, we review the recent progress of graphene oxide-based multifunctional nanomaterials for cancer treatment. A comprehensive and in-depth depiction of unique property of graphene oxide-based multifunctional nanomaterials is first interpreted, with particular descriptions about the suitability for applying in cancer therapy. Afterward, recently emerging representative applications of graphene oxide-based multifunctional nanomaterials in antitumor therapy, including as an ideal carrier for drugs/genes, phototherapy, and bioimaging, are systematically summarized. Then, the biosafety of the graphene oxide-based multifunctional nanomaterials is reviewed.
Conclusions
Finally, the conclusions and perspectives on further advancing the graphene oxide-based multifunctional nanomaterials toward potential and versatile development for fundamental researches and nanomedicine are proposed.
Graphic abstract
Osteoarthritis (OA) is a common degenerative joint disease that can lead to disability. Blocking the complex malignant feedback loop system dominated by oxidative stress and pro-inflammatory factors ...is the key to treating OA. Here, we develop a multifunctional composite thermo-sensitive hydrogel (HPP@Cu gel), which is utilized by Poloxamer 407 (P407) and hyaluronic acid (HA) mixture as the gel matrix, then physically mixed with copper nanodots (Cu NDs) and platelet-rich plasma (PRP). Cu NDs is a novel nano-scavenger of reactive oxygen and nitrogen species (RONS) with efficient free radical scavenging activity. HPP@Cu gel is injected into the articular cavity, where it form an in situ gel that slowly released Cu NDs, HA, and PRP, prolonging the duration of drug action. Our results indicate that HPP@Cu gel could efficiently remove RONS from inflammatory sites and promote repolarization of macrophages to an anti-inflammatory phenotype. The HPP@Cu gel therapy dramatically reduces cartilage degradation and inflammatory factor production in OA rats. This study provides a reliable reference for the application of injectable hydrogels in inflammatory diseases associated with oxidative stress.
Multidrug resistance (MDR) has been restricting the efficacy of chemotherapy, which mainly include pump resistance and non-pump resistance. In order to fight overall MDR, a novel targeted gene/drug ...co-deliver nano system is developed, which can suppress the drug efflux pumps and modulate autophagy to overcoming both pump and non-pump resistance. Here, small interfere RNA (siRNA) is incorporated into polymer-drug conjugates (PEI-PTX, PP) which are composed of polyethyleneimine (PEI) and paclitaxel (PTX) via covalent bonds, and hyaluronic acid (HA) is coated on the surface of PP/siRNA to achieve long blood cycle and CD44-targeted delivery. The RNA interference to mdr1 gene is combined with autophagy inhibition by PP, which efficiently facilitate apoptosis of Taxol-resistant lung cancer cells (A549/T). Further study indicates that PEI in PP may play a significant role to block the autophagosome-lysosome fusion process by means of alkalizing lysosomes. Both in vitro and in vivo studies confirm that the nanoassemblies can successfully deliver PTX and siRNA into tumor cells and significantly inhibited A549/T tumor growth. In summary, the polymeric nanoassemblies provide a potential strategy for combating both pump and non-pump resistance via the synergism of RNAi and autophagy modulation.
A low cytotoxicity and high efficiency delivery system with the advantages of low cost and facile fabrication is needed for the application of small interfering RNA (siRNA) delivery both in vitro and ...in vivo. For these prerequisites, cationic polymer-mesoporous silica nanoparticles (ssCP-MSNs) were prepared by surface functionalized mesoporous silica nanoparticles with disulfide bond cross-linked poly(2-dimethylaminoethyl methacrylate) (PDMAEMA). In vitro and in vivo evaluations were performed. The synthesized ssCP-MSNs are 100-150 nm in diameter with a pore size of 10 nm and a positively charged surface with a high zeta potential of 27 mV. Consequently, the ssCP-MSNs showed an excellent binding capacity for siRNA, and an enhancement in the cell uptake and cytosolic availability of siRNA. Furthermore, the intracellular reducing cleavage of the disulfide bonds cross-linking the PDMAEMA segments led to intracellular cleavage of PDMAEMA from ssCP-MSNs, which facilitated the intracellular triggered release of siRNA. Therefore, promoted RNA interference was observed in HeLa-Luc cells, which was equal to that of Lipofectamine 2000. Significantly, compared to Lipofectamine 2000, the ssCP-MSNs were more biocompatible, with low cytotoxicity (even non-cytotoxicity) and promotion of cell proliferation to HeLa-Luc cells. The in vivo systemic distribution studies certified that ssCP-MSNs/siRNA could prolong the duration of siRNA in vivo, and that they accumulated in the adrenal gland, liver, lung, spleen, kidney, heart and thymus after intravenous injection. Encouragingly, with the ability to deliver siRNA to a tumor, ssCP-MSNs/siRNA showed a tumor suppression effect in the HeLa-Luc xenograft murine model after intravenous injection. Therefore, the ssCP-MSNs cationic polymer-mesoporous silica nanoparticles with low cytotoxicity are promising for siRNA delivery.
With the development of nanotechnology, self-assembled chitosan/phospholipid nanoparticles (SACPNs) show great promise in a broad range of applications, including therapy, diagnosis, in suit imaging ...and on-demand drug delivery. Here, a brief review of the SACPNs is presented, and its critical underlying formation mechanisms are interpreted with an emphasis on the intrinsic physicochemical properties. The state-of-art preparation methods of SACPNs are summarized, with particular descriptions about the classic solvent injection method. Then SACPNs microstructures are characterized, revealing the unique spherical core-shell structure and the drug release mechanisms. Afterwards, a comprehensive and in-depth depiction of their emerging applications, with special attention to drug delivery areas, are categorized and reviewed. Finally, conclusions and outlooks on further advancing the SACPNs toward a more powerful and versatile platform for investigations covering from fundamental understanding to developing multi-functional drug delivery systems are discussed.
Synergistic therapy of tumor is a promising way in curing cancer and in order to achieve effective tumor therapy with real-time drug release monitoring, dynamic cellular imaging and antitumor ...activity.
In this work, a polymeric nanoparticle with Forster resonance energy transfer (FRET) effect and chemo-photodynamic properties was fabricated as the drug vehicle. An amphiphilic polymer of cyclo(RGDfCSH) (cRGD)-poly(ethylene glycol) (PEG)-Poly(L-histidine) (PH)-poly(ε-caprolactone) (PCL)-Protoporphyrin (Por)-acting as both a photosensitizer for photodynamic therapy (PDT) and absorption of acceptor in FRET was synthesized and self-assembled into polymeric nanoparticles with epirubicin (EPI)-acting as an antitumor drug for chemotherapy and fluorescence of donor in FRET. Spherical EPI-loaded nanoparticles with the average size of 150 ± 2.4 nm was procured with negatively charged surface, pH sensitivity and high drug loading content (14.9 ± 1.5%). The cellular uptake of EPI-loaded cRGD-PEG-PH-PCL-Por was monitored in real time by the FRET effect between EPI and cRGD-PEG-PH-PCL-Por. The polymeric nanoparticles combined PDT and chemotherapy showed significant anticancer activity both in vitro (IC
= 0.47 μg/mL) and better therapeutic efficacy than that of free EPI in vivo.
This work provided a versatile strategy to fabricate nanoassemblies for intracellular tracking of drug release and synergistic chemo-photodynamic therapy.
Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in Deep Tissue Injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, ...curcumin is unstable under acidic and alkaline conditions and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy.
This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models.
CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing.
The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than the other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation. In contrast, control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylated-STAT3.
Our results showed that CPNPs enhanced wound healing in DTI models through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.
In recent years, the incidence of various types of tumors has gradually increased, and it has also been found that there is a certain correlation between abnormal glucose and lipid metabolism and ...tumors. Glycolipid metabolism can promote tumor progression through multiple pathways, and the expression of related genes also directly or indirectly affects tumor metabolism, metastasis, invasion, and apoptosis. There has been much research on targeted drug delivery systems designed for abnormal glucose and lipid metabolism due to their accuracy and efficiency when used for tumor therapy. In addition, gene mutations have become an important factor in tumorigenesis. For this reason, gene therapy consisting of drugs designed for certain specifically expressed genes have been transfected into target cells to express or silence the corresponding proteins. Targeted gene drug vectors that achieve their corresponding therapeutic purposes are also rapidly developing. The genes related to glucose and lipid metabolism are considered as the target, and a corresponding gene drug carrier is constructed to influence and interfere with the expression of related genes, so as to block the tumorigenesis process and inhibit tumor growth. Designing drugs that target genes related to glucose and lipid metabolism within tumors is considered to be a promising strategy for the treatment of tumor diseases. This article summarizes the chemical drugs/gene drug delivery systems and the corresponding methods used in recent years for the treatment of abnormal glucose and lipid metabolism of tumors, and provides a theoretical basis for the development of glucolipid metabolism related therapeutic methods.
We, the Editors and Publisher of the journal Artificial Cells, Nanomedicine, and Biotechnology, have retracted the following article:
Wenxue Tian, Shangcong Han, Xia Huang, Mei Han, Jie Cao, Yan ...Liang & Yong Sun (2019) LDH hybrid thermosensitive hydrogel for intravaginal delivery of anti-HIV drugs. Artificial Cells, Nanomedicine, and Biotechnology, 47:1, 1234-1240, DOI:
10.1080/21691401.2019.1596935
Since publication, concerns were raised about Figure 3. When approached for an explanation, the authors have been unable to provide a satisfactory response. We are therefore retracting this article and the corresponding author listed in this publication has been informed.
We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.
The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as 'Retracted'.
Platinum(II)-based drugs (PtII), which hinder DNA replication, are the most widely used chemotherapeutics. However, current PtII drugs often miss their DNA targets, leading to severe side effects and ...drug resistance. To overcome this challenge, we developed a oxaliplatin-based platinum(IV) (PtIV) prodrug amphiphile (C16-OPtIV-R8K), integrating a long-chain hydrophobic lipid and a nucleus-targeting hydrophilic peptide (R8K). This design allows the prodrug to self-assemble into highly uniform lipid nanoparticles (NTPtIV) for enhanced targeting chemotherapy and immunotherapy. Subsequently, NTPtIV's bioactivity and effects were examined at diverse levels, encompassing cancer cells, 3D tumor spheres, and in vivo. Our in vitro studies show a 74% cancer cell nucleus localization of platinum drugs-3.6 times higher than that of oxaliplatin, achieving more than a ten-fold increase in eliminating drug-resistant cancer cells. In vivo, NTPtIV shows efficient tumor accumulation, leading to suppressed tumor growth of murine breast cancer. Moreover, NTPtIV recruited more CD4+ and CD8+ T cells and reduced CD4+ Foxp3+ Tregs to synergistically enhance targeted chemotherapy and immunotherapy. Overall, this strategy presents a promising advancement in nucleus-targeted cancer therapy, synergistically boosting the efficacy of chemotherapy and immunotherapy.
Nucleus-targeted Pt lipid nanoparticles (NTPtIV) assembled by amphipathic PtIV prodrug (C16-OPtIV-R8K) with 74% efficiency to enable accumulation of Pt drugs in the cancerous nucleus for enhanced targeted chemotherapy and immunotherapy. Display omitted
•A novel PtIV prodrug amphiphile (C16-OPtIV-R8K) for nucleus-targeting.•Nano-assembly nucleus-targeted PtIV lipid nanoparticles NTPtIV with 74% efficiency was obtained.•NTPtIV improves the endocytosis and nuclear targeting efficiency of Pt via lipidation and R8K.•NTPtIV induces cancer cell death and reverses Pt-based drug resistance for targeted chemotherapy and enhanced immunotherapy.
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