Preoperative localization of the tumor sites and intraoperative real-time monitoring are essential for precise surgery but are meanwhile challenging due to the lack of high-resolution, easy-to-operate, and fast visualization techniques. On the other hand, tumor recurrence and metastasis after surgery greatly reduce the survival rate of patients. Intervening tumor recurrence during surgery is a future direction of tumor treatment. Nanomaterials with external condition responsiveness (light, ultrasound, and magnetic field) can accurately assist intraoperative detection and surgical resection due to their functions such as tumor cell targeting, fluorescence imaging, and real time monitoring, providing a more accurate, shorter duration, and visualization method of surgical resection. Moreover, nanomaterials are versatile and can easily be tailored for application in different tumors. Locally filled or systemically circulating nanomaterials with slow drug release and residual tumor cell-targeting ability have promising applications in inhibiting tumor recurrence. Here, we review surgical navigation and postoperative recurrence interventional nanomaterials and their landscape in guiding tumor treatment. We summarize the classification and characteristics of these nanomaterials and discuss their application in the surgical navigation and recurrence inhibition of different tumors. We also provide an outlook on the challenges and future development of nanomaterials for visualized tumor surgical navigation and postoperative recurrence inhibition.

Precise imaging is essential for the accurate diagnosis and surgical guidance of brain diseases but it is challenging due to the difficulties in crossing the blood-brain barrier (BBB), the difficulties in disease lesion targeting, and the limited contrast in the brain environment. Nano-imaging agents were characterized by functionalized modifications, high contrast, small size, and high biocompatibility, thus providing advantages in BBB crossing, brain targeting, imaging resolution, and real-time monitoring, holding great potential in brain disease imaging. Specific characteristics in brain environment and brain diseases (e.g., marker proteins on the BBB, the pathogenic proteins in the neurodegenerative diseases or brain tumors, and the tumor and inflammatory microenvironment) provide opportunities for the functionalized nano-imaging agents to improve BBB crossing and disease targeting. Moreover, the versatile nano-imaging agents are endowed with therapeutic agents to facilitate the theranostics of brain diseases. Here, we summarized the common materials and imaging techniques of nano-imaging agents and their imaging treatment applications. We discussed their BBB penetration, environmental response for disease targeting, and therapeutic effects. We also provided insights on the advantages, challenges, and application of nano-imaging agents in detecting and treating brain diseases such as neurodegenerative diseases, brain tumors, stroke, and traumatic brain injury. These discussions will help develop nano-imaging agents-based theranostic platforms for the precise diagnosis and treatment of brain diseases.

Cell membrane-engineered nano-delivery systems have evolved as a promising strategy to enhance drug bioavailability, offering an alternative for reversing drug resistance in cancer therapy. Herein, a formulated nano-liposome that fabricated by hybridizing cisplatin-resistant A549 cell line (A549/cis) cancer cell membrane and phospholipids for co-delivery of cisplatin and nuclear protein zeste homolog 2 (EZH2)-targeting peptide EIP103, referred to as cLCE, was developed. In vitro results indicated that the formulated nano-liposome can efficiently inhibit A549/cis cancer cell invasion and metastasis through the down-regulation of N-cadherin and vimentin proteins. Mechanistic studies demonstrated that the reduction of nerve growth factor receptor (NGFR) levels and the increase of peroxisome proliferator-activated receptor γ (PPARγ) levels achieved by EIP103 may contribute to the reversal of cisplatin resistance. In vivo results demonstrated that the encapsulation of both cisplatin and EIP103 within cLCE leads to increased intratumoral accumulation and prolonged survival in A549/cis cancer-bearing mice as compared to the individual drugs alone. This can be attributed to the enhanced tumor homing capability of cLCE achieved through the presence of inherited membrane proteins derived from A549/cis cells. Taken together, this study may provide a highly promising therapeutic strategy to improve clinical treatments for cisplatin-resistance non-small-cell lung cancer (NSCLC) as well as other malignant cancers.

Chemotherapy remains one of the most prevailing strategies for cancer treatment. However, its treatment effect is hampered by drug resistance, nonspecific tumor targeting, and severe toxic side effects. Combination chemotherapy with synergistic effect has become an attractive tumor therapy. N⁶-methyladenosine (m⁶A) regulators determine the fate of m⁶A-modified transcripts and play vital roles in cancer development and drug resistance. Gene therapy such as small interfering RNA (siRNA) is a promising strategy to reduce the abnormal gene expression of m⁶A regulators. However, its poor selectivity and high systemic toxicity necessitate the use of delivery vectors to target specific cells and tissues. Here, we constructed a dual-functional targeted nanodrug platform for the synergetic m⁶A-associated epigenetic regulation and chemotherapy of ovarian cancer. We encapsulated siRNA targeting the m⁶A reader YT521-B homology (YTH) N⁶-methyladenosine RNA-binding protein 1 (YTHDF1) and docetaxel (DTX), the first-line chemotherapeutic agent of ovarian cancer, into mesenchymal stem cell-derived small extracellular vesicles (MsEVs). This nanosystem exhibits significant tumor targeting and endo/lysosomal escape of siYTHDF1. It effectively depletes YTHDF1 and suppresses the protein translation of eukaryotic translation initiation factor 3 subunit C (EIF3C) in an m⁶A-dependent manner. The combination of YTHDF1-targeting epigenetic regulation significantly enhances the anti-tumor effect of DTX and effectively inhibits ovarian cancer progression without causing significant systemic toxicity. This co-delivery nanoplatform offers a promising approach for combinational cancer treatment, showing improved anti-tumor efficacy through the synergistic effects of epigenetic regulation and chemotherapeutic inhibition.

We have determined the binding strengths between ribonucleotides of adenine (A), guanine (G), uracil (U), and cytosine (C) in homogeneous single-stranded ribonucleic acids (ssRNAs) and homo-decapeptides consisting of 20 common amino acids. We use a bead-based fluorescence assay for these measurements in which decapeptides are immobilized on the bead surface and ssRNAs are in solutions. The results provide a molecular basis for analyzing selectivity, specificity, and polymorphisms of amino-acid–ribonucleotide interactions. Comparative analyses of the distribution of the binding energies reveal unique binding strength patterns assignable to each pair of amino acid and ribonucleotide originating from the chemical structures. Pronounced favorable (such as Arg–G) and unfavorable (such as Met–U) binding interactions can be identified in selected groups of amino acid and ribonucleotide pairs that could provide basis to elucidate energetics of amino-acid–ribonucleotide interactions. Such interaction selectivity, specificity, and polymorphism manifest the contributions from RNA backbone, RNA bases, as well as main chain and side chain of the amino acids. Such characteristics in peptide–RNA interactions might be helpful for understanding the mechanism of protein–RNA specific recognition and the design of RNA nano-delivery systems based on peptides and their derivatives.

For the design and optimization of functional peptides, unravelling the structures of individual building blocks as well as the properties of the ensemble is paramount. TTR1, derived from human transthyretin, is a fibril-forming peptide implicated in diseases such as familial amyloid polyneuropathy and senile systemic amyloidosis. The functional peptide TTR1-RGD, based on a TTR1 scaffold, was designed to specifically interact with cells. Here, we used scanning tunneling microscopy (STM) to analyze the assembly structures of TTR1-related peptides with both the reverse sequence and the modified forward sequence. The sitespecific analyses show the following: ⅰ) The TTR1 peptide is involved in assembly, nearly covering the entire length within the ordered β-sheet structures. ⅱ) For TTR1-RGD peptide assemblies, the TTR1 motif forms the ordered β-sheet while the RGDS motif adopts a flexible conformation allowing it to promote cell adhesion. The key site is clearly identified as the linker residue Gly13. ⅲ) Close inspection of the forward and reverse peptide assemblies show that in spite of the difference in chemistry, they display similar assembling characteristics, illustrating the robust nature of these peptides. iv) Glycine linker residues are included in the β-strands, which strongly suggests that the sequence could be optimized by adding more linker residues. These garnered insights into the assembled structures of these peptides help unravel the mechanism driving peptide assemblies and instruct the rational design and optimization of sequenceprogrammed peptide architectures.