化学疗法仍是各种肿瘤类型中的主要治疗方法，通常伴随着转移导致预后不佳。搭载CREKA靶向部分的PEG化脂质体是众所周知的治疗剂，尤其是在高度转移实验模型中。CREKA特异性靶向肿瘤相关ECM，该ECM存在于原发瘤和转移瘤部位。为了更好地理解靶向部分的功能，我们决定设计不同量的靶向部分附着在它们的DSPE-PEG分子上的各种脂质体制剂。此外，设计了新的肿瘤归巢性五肽（SREKA），以及SREKA和DSPE-PEG之间的新型连接策略。首先，研究了药物载荷脂质体的体外增殖抑制和其载荷的细胞摄取。之后，测量了小鼠血液中脂质体的稳定性和不同组织中的药物积累。此外，还检查了不同脂质体制剂的体内肿瘤生长和转移抑制能力。根据我们的比较研究，SREKA-脂质体在制剂后具有均一的表型，并具有类似的特性和肿瘤归巢能力，与CREKA-脂质体相似。然而，在连接中将N-端半胱氨酸换成丝氨酸，可以获得更高的产量和更好的稳定性。我们还表明，DSPE-PEG附着的靶向部分的数量在脂质体的稳定性中起着重要作用，因此它在毒性和靶向方面发挥重要作用。此外，我们提供了证据表明，SREKA-脂质体可以显著抑制原发肿瘤的生长和转移发生率，增加携带肿瘤的小鼠的存活率。

Chemotherapy is still a leading therapeutic approach in various tumor types that is often accompanied by a poor prognosis because of metastases. PEGylated liposomes with CREKA targeting moiety are well-known therapeutic agents, especially in highly metastatic experimental models. CREKA specifically targets tumor-associated ECM, which is present at the primary, as well as metastatic tumor sites. To better understand the function of the targeting moieties, we decided to design various liposome formulations with different amounts of targeting moiety attached to their DSPE-PEG molecules. Moreover, a new tumor-homing pentapeptide (SREKA) was designed, and a novel conjugation strategy between SREKA and DSPE-PEGs. First, the in vitro proliferation inhibition of drug-loaded liposomes and the cellular uptake of their cargo were investigated. Afterward, liposome stability in murine blood and drug accumulation in different tissues were measured. Furthermore, in vivo tumor growth, and metastasis inhibition potencies of the different liposome formulations were examined. According to our comparative studies, SREKA-liposomes have a uniform phenotype after formulation and have similar characteristics and tumor-homing capabilities to CREKA-liposomes. However, the exchange of the N-terminal cysteine to serine during conjugation results in a higher production yield and better stability upon conjugation to DSPE-PEGs. We also showed that SREKA-liposomes have significant inhibition on primary tumor growth and metastasis incidence; furthermore, increase the survival rate of tumor-bearing mice. Besides, we provide evidence that the amount of targeting moiety attached to DSPE-PEGs is largely responsible for the stability of liposomes, therefore it plays an important role in toxicity and targeting.