Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.
There has been growing interest in the research of nanomaterials for biomedical applications in recent decades. Herein, a simple approach to synthesize the G4.5-GdO-poly(ethylene glycol) (G4.5-GdO-PEG) nanoparticles (NPs) that demonstrate potential as dual (T and T) contrasting agents in magnetic resonance imaging (MRI) has been reported in this study. Compared to the clinically popular Gd-DTPA contrasting agents, G4.5-GdO-PEG NPs exhibited a longer longitudinal relaxation time (T) and better biocompatibility when incubated with macrophage cell line RAW264.7 in vitro. Furthermore, the longitudinal relaxivity (r) of G4.5-GdO-PEG NPs was 53.9 s mM at 7T, which is equivalent to 4.8 times greater than to the Gd-DTPA contrasting agents. An in vivo T-weighted MRI results revealed that G4.5-GdO-PEG NPs significantly enhanced signals in the intestines, kidney, liver, bladder, and spleen. In addition, the T-weighted MRI results revealed darker contrast in the kidney, which proves that G4.5-GdO-PEG NPs can be exploited as T and T contrasting agents. In summary, these findings suggest that the G4.5-GdO-PEG NPs synthesized by an alternative approach can be used as dual MRI contrasting agents.
In this study, PAMAM dendrimer (G4.5) was conjugated with two targeting moieties, IL-6 antibody and RGD peptide (G4.5-IL6 and G4.5-RGD conjugates). Doxorubicin anticancer drug was physically loaded onto G4.5-IL6 and G4.5-RGD with the encapsulation efficiency of 51.3 and 30.1% respectively. The cellular internalization and uptake efficiency of G4.5-IL6/DOX and G4.5-RGD/DOX complexes was observed and compared by confocal microscopy and flow cytometry using HeLa cells, respectively. The lower IC50 value of G4.5-IL6/DOX in comparison to G4.5-RGD/DOX is indication that higher drug loading and faster drug release rate corresponded with greater cytotoxicity. The cytotoxic effect was further verified by increment in late apoptotic/necrotic cells due to delivery of drug through receptor-mediated endocytosis. On the basis of these results, G4.5-IL6 is a better suited carrier for targeted drug delivery of DOX to cervical cancer cells.
In the last few decades, cancer immunotherapy becomes an important tactic for cancer treatment. However, some immunotherapy shows certain limitations including poor therapeutic targeting and unwanted side effects that hinder its use in clinics. Recently, several researchers are exploring an alternative methodology to overcome the above limitations. One of the emerging tracks in this field area is nano-immunotherapy which has gone through rapid progress and revealed considerable potentials to solve limitations related to immunotherapy. Targeted and stimuli-sensitive biocompatible nanoparticles (NPs) can be synthesized to deliver immunotherapeutic agents in their native conformations to the site of interest to enhance their antitumor activity and to enhance the survival rate of cancer patients. In this review, we have discussed cancer immunotherapy and the application of NPs in cancer immunotherapy, as a carrier of immunotherapeutic agents and as a direct immunomodulator.
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