An update in the applications of exosomes in cancer theranostics: from research to clinical trials.

Exosomes are nanosized extracellular vesicles secreted by nearly all viable cells following the fusing of multivesicular bodies and the plasma membrane and discharged into the encircling bodily fluids. Exosomes can transport cell-specific components from the source cell to the target cell. Given the enormous potential of exosomes as non-invasive diagnostic biomarkers and therapeutic nanovehicles. Lately, accumulated evidence has demonstrated that exosomes serve an important role in prognosis, diagnosis, and even treatment strategies. While several reviews have collective information on the biomedical application of exosomes, a comprehensive review incorporating updated and improved methodologies for beneficial applications of such vesicles in cancer theranostics is indispensable. In the current review, we first provided a comprehensive review of the introduction of exosomes, featuring their discovery, separation, characterization, function, biogenesis, secretion. The implications of exosomes as promising nanovehicles for drug and gene delivery, application of exosome inhibitors in the management of cancers, completed and ongoing clinical trials on the biological relevance of exosomes are then discussed in detail. As the field of exosome research grows, a better understanding of the subcellular parts and mechanisms involved in exosome secretion and targeting of specific cells will help figure out what their exact physiological functions are in the body.

Design of an efficient fluorescent nanoplatform carrier for hydrophobic drugs along with green carbon dot: Possible application in cancer image-guided drug therapy.

Nanotechnology has taken novel approaches to advance cancer therapeutic efficacy employing multifunctional nanocarriers with drug delivery and imaging function. In this work, we designed a biocompatible and affordable fluorescence nanocarrier called chitosan (CS)-carbon dot (CD) hybrid nanogel for cell imaging. The green CDs were synthesized using tomato juice through a simple single-step hydrothermal method. Chitosan polymer was used as a carrier for co-delivery CDs and the anti-cancer drug with low solubility, silibinin (Sil), to design the Sil-chitosan carbon dots hybrid nanogels (CCHNs) system. After optimizing the physicochemical properties of nanostructure by DLS, FTIR, FESEM, TEM, and UV-visible techniques, the successful uptake of the fluorescent nanoparticle conjugates into MCF-7 breast cancer cells occurred. Then we embedded CDs in chitosan nanogel. The resultant CCHNs demonstrated optical properties similar to free-CDs, a desirable size distribution (55.22 nm) with a positive surface charge, a suitable loading capacity for Sil (35%), and drug release vulnerable to pH changes. The fluorescent nanocarrier could transfer Sil to MCF-7 cancer cells without remarkable toxicity. The results of the fluorescent microscope indicated that after 4 h, the solid fluorescent signal was received from cells containing CCHNs compared to free CDs and confirmed the ability of hybrid nanogels to high cellular uptake. This study demonstrates a multifunctional nanocarrier containing therapeutic compounds and fluorescent agents that provide cellular imaging to enhance therapeutic efficacy.

An Updated Review on Implications of Autophagy and Apoptosis in Tumorigenesis: Possible Alterations in Autophagy through Engineered Nanomaterials and Their Importance in Cancer Therapy.

Most commonly recognized as a catabolic pathway, autophagy is a perplexing mechanism through which a living cell can free itself of excess cytoplasmic components, i.e., organelles, by means of certain membranous vesicles or lysosomes filled with degrading enzymes. Upon exposure to external insult or internal stimuli, the cell might opt to activate such a pathway, through which it can gain control over the maintenance of intracellular components and thus sustain homeostasis by intercepting the formation of unnecessary structures or eliminating the already present dysfunctional or inutile organelles. Despite such appropriateness, autophagy might also be considered a frailty for the cell, as it has been said to have a rather complicated role in tumorigenesis. A merit in the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. In fact, several investigations on tumorigenesis have reported diminished levels of autophagic activity in tumor cells, which might result in transition to malignancy. On the contrary, autophagy has been suggested to be a seemingly favorable mechanism to progressed malignancies, as it contributes to survival of such cells. Based on the recent literature, this mechanism might also be activated upon the entry of engineered nanomaterials inside a cell, supposedly protecting the host from foreign materials. Accordingly, there is a good chance that therapeutic interventions for modulating autophagy in malignant cells using nanoparticles may sensitize cancerous cells to certain treatment modalities, e.g., radiotherapy. In this review, we will discuss the signaling pathways involved in autophagy and the significance of the mechanism itself in apoptosis and tumorigenesis while shedding light on possible alterations in autophagy through engineered nanomaterials and their potential therapeutic applications in cancer. SIGNIFICANCE STATEMENT: Autophagy has been said to have a complicated role in tumorigenesis. In the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. On the contrary, autophagy has been suggested to be a favorable mechanism to progressed malignancies. This mechanism might be affected upon the entry of nanomaterials inside a cell. Accordingly, therapeutic interventions for modulating autophagy using nanoparticles may sensitize cancerous cells to certain therapies.

Genomic Instability in Cancer: Molecular Mechanisms and Therapeutic Potentials.

DNA damage usually happens in all cell types, which may originate from endogenous sources (i.e., DNA replication errors) or be emanated from radiations or chemicals. These damages range from changes in few nucleotides to significant structural abnormalities on chromosomes and, if not repaired, could disturb the cellular homeostasis or cause cell death. As the most significant response to DNA damage, DNA repair provides biological pathways by which DNA damages are corrected and returned into their natural circumstance. However, an aberration in the DNA repair mechanisms may result in genomic and chromosomal instability and the accumulation of mutations. The activation of oncogenes and/or inactivation of tumor suppressor genes is a serious consequence of genomic and chromosomal instability and may bring the cells into a cancerous phenotype. Therefore, genomic and chromosomal instability is usually considered a crucial factor in carcinogenesis and an important hallmark of various human malignancies. In the present study, we review our current understanding of the most updated mechanisms underlying genomic instability in cancer and discuss the potential promises of these mechanisms in finding new targets for the treatment of cancer.

New insight into the engineering of green carbon dots: Possible applications in emerging cancer theranostics.

Fluorescence imaging via carbon dots (CDs) has found multifarious applications in the biomedical sciences including biosensing, cancer cell bioimaging, drug delivery and tracking therapeutic response. Presently, the latest generation of fluorescence CDs known as green-CDs has attracted ever-increasing attention due to the use of natural sources, low-cost synthesis, nanoscale size, promising biocompatibility, superior photoluminescence, and ease of functionalization for versatile applications, which in turn could have higher priority over the traditional toxic fluorescent agents. In this review, we aim to have a new insight into the engineering green-CDs and their physicochemical properties. Moreover, we discuss the possible applications of green-CDs in self and active targeting, therapeutics delivery, and finally their promising future in cancer theranostics.