Systemic platelet inhibition with localized chemotherapy by an injectable ROS-scavenging gel against postsurgical breast cancer recurrence and metastasis.

Early solid tumors benefit from surgical resection, but residual stubborn microtumors, pro-inflammatory microenvironment and activated platelets at the postoperative wound site are prone to recurrence and metastasis, resulting in poor prognosis. Here, we developed a dual-pronged strategy consisting of (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs at the postoperative wound site to improve the tumor microenvironment and inhibit the recurrence of residual microtumors after orthotopic surgery, and (ii) systemic administration of clopidegrol via albumin nanoparticles for inhibiting activated platelets in the circulation thus inhibiting tumor remote migration. In a mouse model of postoperative recurrence and metastasis of orthotopic 4T1 breast cancer, the dual-pronged strategy greatly inhibited postoperative orthotopic tumor recurrence and reduced lung metastasis. This work provides an effective strategy for the postoperative intervention and treatment of solid tumors to inhibit postoperative tumor recurrence and metastasis, which has the potential to improve the prognosis and survival of patients with postoperative solid tumors. STATEMENT OF SIGNIFICANCE: Early-stage solid tumors benefit from surgical resection. However, the presence of residual microtumors, pro-inflammatory tumor microenvironment, and activated platelets at the postoperative wound site lead to recurrence and metastasis, ultimately resulting in poor prognosis. Here, we have devised a dual-pronged approach that includes (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs (TM@Gel) at the wound site after surgery to enhance the tumor microenvironment (TME) and hinder the reappearance of residual microtumors, and (ii) systemic administration of clopidegrol through albumin nanoparticles (HHP) for inhibiting activated platelets in the circulation thus impeding tumor distant migration. This work provides a viable option for postoperative intervention and treatment of solid tumors to suppress postoperative tumor recurrence and metastasis.

Chondroitin Sulfate-Derived Paclitaxel Nanocrystal via π-π Stacking with Enhanced Stability and Tumor Targetability.

Nanocrystals with high drug loading have become a viable strategy for solubilizing drugs with poor aqueous solubility. It remains challenging, however, to synthesize nanocrystals with sufficient stability and targeting potential. Here, we report a novel nanocrystal platform synthesized using paclitaxel (PTX) and Fmoc-8-amino-3,6-dioxaoctanoic acid (Fmoc-AEEA)-conjugated chondroitin sulfate (CS) (CS-Fmoc) via π-π stacking to afford a stable formulation with CD44 targetability (PTX NC@CS-Fmoc). The PTX NC@CS-Fmoc exhibited rodlike shapes with an average hydrodynamic size of 173.6 ± 0.7 nm (PDI = 0.11 ± 0.04) and a drug loading of up to 31.3 ± 0.6%. Next, PTX NC@CS-Fmoc was subjected to lyophilization in the absence of cryoprotectants for long-term storage, and after redispersion, PTX NC@CS-Fmoc displayed an average hydrodynamic size of 205.3 ± 2.9 nm (PDI = 0.15 ± 0.01). In murine Panc02 cells, PTX NC@CS-Fmoc showed higher internalization efficiency than that of PTX nanocrystals without CS modification (PTX NC@F127) (P < 0.05) or that of CS-Fmoc micelles (P < 0.05). Moreover, PTX NC@CS-Fmoc appeared to accumulate in both lysosomes and Golgi apparatus, while CS-Fmoc micelles accumulated specifically in the Golgi apparatus. In the orthotopic Panc02 tumor-bearing mice model, PTX NC@CS-Fmoc showed higher tumor-specific accumulation than CS-Fmoc micelles, which also demonstrated comparable tumor growth inhibition as to Nab-PTX. Overall, the CS-Fmoc-derived nanocrystals represent a neat and viable formulation strategy for targeted chemotherapy with great potential for translational studies.

A roadmap to pulmonary delivery strategies for the treatment of infectious lung diseases.

Pulmonary drug delivery is a highly attractive topic for the treatment of infectious lung diseases. Drug delivery via the pulmonary route offers unique advantages of no first-pass effect and high bioavailability, which provides an important means to deliver therapeutics directly to lung lesions. Starting from the structural characteristics of the lungs and the biological barriers for achieving efficient delivery, we aim to review literatures in the past decade regarding the pulmonary delivery strategies used to treat infectious lung diseases. Hopefully, this review article offers new insights into the future development of therapeutic strategies against pulmonary infectious diseases from a delivery point of view.